NO166708B - INTERMEDIATES FOR THE PREPARATION OF ALKANIC ACIDS AND ESTERS THEREOF. - Google Patents

Description

The present invention relates to new compounds of formula

WE

wherein R<1> represents hydrogen or lower alkyl,

R<3> and R<4> represent, independently of each other, lower alkyl or together the alkylene of 2-6 carbon atoms;

Ar<3> means a 6-methoxy-2-naphthyl group, a 4-isobutylphenyl group, a 4-lower alkoxyphenyl group, a 4-difluoromethoxyphenyl group, a 2-thienyl group, a 4-(1-oxo-2-isoindolinyl)- phenyl group, a 4-biphenylyl group or a 4-(tert-butyl)phenyl group.

The compounds are intermediate products in the production of cx-substituted alkanoic acids and their esters. These are represented by the following general formula

wherein Ar represents phenyl, 4-X-phenyl (where X is chloro, fluoro, isobutyl, tert-butyl, phenyl, acetamino, methoxy, difluoromethoxy, ethoxy or 1-oxo-2-isoindolinyl), 2-thienyl or 6-methoxy -2-naphthy1;

R<1> represents hydrogen or lower alkyl,. or Ar and R<1> represent, together with the carbonate pm to which they are attached, an indanyl group;

R<2> represents hydrogen, lower alkyl or lower hydroxyalkyl.

Many of the compounds of general formula (I) are commercially valuable. E.g. is c-(4-isobutylphenyl)propionic acid corresponding to a compound of the general formula (I), where Ar is a 4-isobutylphenyl group, R<1> is a methyl group, and R<2> is a hydrogen atom, known as "Ibuprofen" which is an anti-inflammatory drug, oc-(6-methoxy-2-naphthyl)propionic acid corresponding to a compound of the general formula ((I)), where Ar is a 6-methoxy-2-naphthyl group, R<1 >is a methyl group, and R<2>is a hydrogen atom, known as "Naproxen". α-(4-difluoromethoxyphenyl)isovaleric acid, corresponding to a compound of the general formula (I) in which Ar is a 4-difluoromethoxyphenyl group, R <1> is an isopropyl group and R<2> is a hydrogen atom, is very effective as an acid moiety of pyrethroid insecticides.

The object of the present invention is to provide new intermediates which can be used in the production of compounds with formula II from application 82.0123 which is again divided from application 81.3088.

According to the method in parent application no. 81.3088 for the preparation of an alkanoic acid or its ester which is substituted in the oc position with an aromatic group of the general formula

wherein Ar represents phenyl, 4-X-phenyl (wherein X is chloro, fluoro, isobutyl, tert-butyl, phenyl, acetamino, methoxy, difluoromethoxy, ethoxy or 1-oxo-2-isoindolinyl), 2-thienyl or 6-methoxy -2-naphthyl;R<1>represents hydrogen or lower alkyl, or Ar and R<1>represent together with the carbon atom to which they are attached an indanyl group;R<2>represents hydrogen, lower alkyl or lower hydroxyalkyl, is hydrolyzed a. α-sulfonyloxyketone acetal with the general formula in which R<3> and R<4>, independently of each other represent lower alkyl or together represent the alkylene with 2-6 carbon atoms; R<5> represents lower alkyl, lower haloalkyl, phenyl, lower alkylphenyl, halophenyl, d- or 1-10-camphoryl; and Ar and R<1> are as defined above, except that Ar and R<1> together with the carbon atom to which they are attached may form a tetrahydronaphthalene group, or treated with an agent possessing an affinity for oxygen. The compounds of formula (II) can be synthesized from α-halogen ketones of the general formula

where X denotes a halogen atom, and Ar and R^" are

as stated above,

in the manner shown in the following reaction core:

REACTION FORM

In the above scheme, M denotes an alkali metal and Hal denotes a halogen atom, especially a chlorine atom, and Ar, R<1>, R3, R<4>, R<5> and X are as defined above.

The compound of formula (V) can be easily prepared by exposing a compound of the formula

where R"<*>" and X are as above,

for Friedel-Crafts; reaction with a compound of the formula

where Ar is as defined above,

or by halogenating a compound of the formula

where Ar and Rr are as defined above, in a manner known per se.

The procedure in the reaction scheme is described in detail below.

Step ( V) > ( VI)

This step involves the action of an alkali metal alkoxide (R 3 OM) on the compounds of general formula (V) in the presence of the corresponding alcohol (R 3 OH) and gives an α-hydroxyketone acetate of general formula (VI). In the compound with the general formula (VI) prepared in this step, R 4 is the same as R 3 . Lithium oxides, sodium alkoxides and potassium alkoxides can suitably be used as the alkali metal alkoxide. The use of sodium alkoxides is preferred on; because they are cheap. The amount of the alkali metal alkoxide is generally at least 1 mol per mol of the compound with formula (V), and the reaction can be quickly completed if it is used in an amount of 1.5 to 3 mol per moles of compound of formula (V). The amount of alcohol that must be present at the same time can be at least 1 mol per moles of compound of formula (V). Advantageously, the alcohol is used in excess so that it also serves as a solvent. It is also possible to add an aprotic solvent which does not take part in the reaction, such as diethyl ether, tetrahydrofuran, DMF or 1,2-dimethoxyethane. The reaction proceeds steadily at a temperature of approx. -20°C to approx. 100°C. To make the operation simplest, the reaction is preferably carried out at room temperature to 60°C.

According to another embodiment, this step can be carried out by reacting the compound of formula (V) with the alkali metal alkoxide (R^OM) in an aprotic solvent, such as diethyl ether, tetrahydrofuran or 1,2-dimethoxyethane and gives an epoxy compound of formula (VII ), and then reacting it with an alcohol (R<4>OH) in the presence of a catalytic amount of an alkali metal alkoxide (R 4OM) gives a ct-hydroxyketonacetal (VI) (see Examples 8 and 9). According to this method, a compound of formula (VI), where R<3> is different from R<4>, can also be prepared.

The reaction between the compound of formula (V) and the alkali metal alkoxide (R^OM) can usually be carried out at a temperature of approx. 0°C to approx. 60°C using 1 to 3 mol, per mole compound with. formula (V), of the alkali metal alkoxide. The reaction between the compound of formula (VII) and the alcohol (R 4 OH) can generally be carried out at a temperature of approx. o2c to approx. 100°C using at least one mole,

per moles of the compound of formula (VII) of the alcohol. Preferably, the alcohol is used in excess so that it also serves as a solvent.

According to a further embodiment

the a-halo<g>ene ketone is reacted with the general for-

mel (V) in the presence of a dihydric alcohol, such as ethylene glycol, propylene glycol or 1,3-propanediol with a monosalt of the dihydric alcohol and an alkali metal and gives the α-hydroxyketone acetal of the general formula (VI). This method gives a product corresponding to formula (VI) where R<3> and R<4> together form an alkylene group such as ethylene, propylene or trimethylene (see example 111).

The reaction can generally be carried out at 0°C to 100°C by using at least 1 mol, preferably 1.5 to 3 mol, of the alkali metal dihydric alcohol monosalt in the presence of at least 0.5 mol, preferably 2 to 10 mol, of the divalent alcohol. An aprotic solvent that does not take part can be added. in the reaction, such as diethyl ether, tetrahydrofuran or: 1, 2-dimethoxyethane.

Compounds of formula (VI) obtained in the above step, where Ar is different from the phenyl and 4-chlorophenyl group, and those where R<1> is different from a hydrogen atom are new compounds not described in the literature, and are subject for the present invention.

Typical examples of such compounds (VI) are given below in addition to those shown in the examples. The compound (VI) wherein Ar is 4-prenylphenyl, R 1 is methyl; Ar is N-methylphenothiazinyl, R<1> is hydrogen or methyl; Ar is 1-methylpyrrolyl, R<1> is hydrogen on methyl; Ar is 2-fluoro-4-biphenylyl, R<1> is methyl; Ar is 2-acetyl-amino-4-biphenylyl, R"1" is methyl; Ar is 4-chlorophenyl, .. R"*" is isopropyl; Ar is 3-chloro-4-(3-pyrrolin-1-yl)phenyl, R<1> is methyl.

Step (VI) > (II)

This step involves the action of an O-sulfonylating agent of the formula R 5 -SO 2 -Hal or (R 5 SO 2 ) 2 ° on the α-hydroxyketone acetal of formula (VI) obtained in the previous step to form the compounds of the general formula

(II).

Examples of the O-sulfonylating agent include sulfonyl halides substituted with an aromatic group, such as benzenesulfonyl chloride, p-toluenesulfonyl chloride, p-bromobenzenesulfonyl chloride, p-nitrobenzenesulfonyl chloride and naphthalene sulfonyl chloride; and alkanesulfonyl halides or alkanesulfonyl anhydrides, such as methanesulfonyl chloride, butanesulfonyl chloride, methanesulfonyl anhydride,. trifluoromethanesulfonyl anhydride, trifluoromethanesulfonyl chloride, d-10-camphorsulfonyl chloride, and /-10-camphorsulfonyl chloride.

The reaction can preferably be carried out under neutral to basic conditions, and from this point of view the reaction is advantageously carried out in the presence of at least 1 mol, per moles of for the bond of formula (VI), of a tertiary amine such as triethylamine, pyridine, or 4-dimethylaminopyridine. In this way, the reaction can be carried out at a relatively low temperature of from approx. 0°C to room temperature. It is also possible to add an aprotic solvent, which does not take part in the reaction, such as methylene chloride or diethyl ether.

As described above, the compound of the general formula (II) can be prepared in two steps from α-halo-

the gene ketone of the general formula (V). It can also be prepared according to other methods, such as a method which consists in oxidizing a 1-(aromatic group)-1-alkoxy-1-alkene with the formula

1 3

where Ar, R and R are as above,

to form the epoxy compound of formula (VII), prepare the α-hydroxyketone acetal of formula (VI) from the epoxy compound as above, and furthermore carry out step (VI) ► (II) ; ; a method which consists in acetalizing the corresponding

the α-sulfonyloxyketone of the compound of the general formula (II); and a method comprising reducing an a-oxo-

13 4

where Ar, R , R and R are as defined above,

to form the α-hydroxyketone acetal of formula (VI), and subject it to step (VI) > (II).

Thus, the α-sulfonyloxyketone acetal of formula (II) can be prepared according to various easy methods with a smaller number of steps.

The compounds of formula (I) include many compounds

bonds applicable in such areas as pharmaceuticals and agricultural chemicals. Typical examples of such applicable compounds

are "Ibuprofen", "Naproxen" and α-[4-(1-oxo-2-isoindolinyl)-phenyl]propionic acid (anti-inflammatory agent, "Indoprofen"). Typical examples also include α-(2-thienyl)propionic acid, methyl α-(4-acetylaminophenyl)propionate, α-[4-(tert-butyl)-phenyl]isovaleric acid, methyl α-(4-alkoxyphenyl)isovalera -ter, α-(4-biphenylyl)propionic acid, methyl-α-(4-difluoromethoxy-phenyl) isovalerate, and methyl-α-(4-alkoxyphenyl) propionates which are known as important synthetic intermediates for anti-inflammatory agents and insecticides.

The following examples illustrate the present invention

see more detail.

EXAMPLE 1

9.81 g of p-toluenesulfonyl chloride was dissolved in 10 ml of anhydrous pyridine and the mixture was stirred at room temperature. The solution was added dropwise over 10 min. 10 ml of an anhydrous pyridine solution of 6.65 g of α-hydroxypropiophenone-dimethyl acetal and the mixture was stirred for 48 hl. The reaction mixture was poured into 200 ml of ice water and stirred for 2 h. The resulting precipitate was collected by filtration, washed with water and dried under vacuum over potassium hydroxide and gave 10.91 g of α-(p-toluenesulfonyloxy)propiophenone-dimethyl acetal as colorless crystals.

Yield: 92%

Melting point: 62 - 63 C (from naphtha)

IR (KBr): 1360, 1190, 1175, 1090, 1060, 1040, 910,

710 cm"<1.>

NMR (CDCl 3 ) : <S"1.07 (3H, d, J=6Hz), 2.73 (3H, s) ,

3.08 (3H, s), 3.15 (3H, s), 4.95 (1H, q, J=6Hz), 7.33 (7H, m), 7.77 (2H, d, J=9Hz).

For C18H22<0>5<S:>

Calculated: C, 61.70; H, 6.33; S, 9.15%.

Found: C, 61.72; H, 6.26; S, 9.19%.

EXAMPLE 2

19.0 g of p-isobutylpropiophenone was dissolved in a mixture of 15 ml of anhydrous diethyl ether and 5 ml of anhydrous dioxane, and the solution was stirred at room temperature. Bromine (17.6 g) was added dropwise over 25 min. and the mixture was stirred for 2.5 h. Water (50 mL) was added and the mixture was extracted with 20 mL of diethyl ether 3 times. The extract was washed with 50 ml of water 4 times, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was dissolved in 30 ml of hot methanol and cooled to -40°C. The precipitate was collected by filtration and washed with cold methanol to give 21.88 g of α-bromo-p-isobutylpropiophenone as colorless crystals.

Yield: 81%

M.p.: 63 - 66°C

IR(KBr): 2950, 1680, 1608, 1419, 1260, 1250, 1167, 955, 862 cm"<1>.

NMR (CDCl 3 ): <S 0.91 (6H, d, J=7Hz), 1.87 (3H, d,

J=7Hz), 1.8 - 2.2 (1H, m), 2.52 (2H, d, J=7Hz), 5.25 (1H, q, J=7Hz), 7.22 (2H, d, J=9Hz), 7.92 (2H, d, J=9Hz).

For C13H:i7<O>Br:

Calculated: C,. 58.00; H, 6.37; Br, 29.69% Found: C, 57.80; H, 6.27; Br, 29.42%

EXAMPLE 3

Sodium methoxide (1.134 g) was dissolved in 20 ml of anhydrous methanol and the solution was stirred at room temperature in an atmosphere of argon. To the solution was added dropwise over 30 min. at room temperature 20 ml of an anhydrous methanol solution of 2.692 g of α-bromo-p-isobutylpropiophenone. After the addition, 50 ml of water was added to the reaction mixture,

and the mixture was extracted with 20 ml of diethyl ether 3 times. The extract was washed with 20 ml of water, dried over anhydrous magnesium sulfate and potassium carbonate and concentrated under reduced pressure in the presence of a small amount of potassium carbonate to give 2.370 g of α-hydroxy-p-isobutylpropiophenone -dimethyl acetal as a colorless; oily substance. The yield was 94%.

For elemental analysis, the product was purified by column chromatography (Florisil; methylene chloride).

IR (pure): 3500, 2950, 1460, 1100, 1050, 980, 850,

800, 740 cm"<1>.

NMR (CDG.l ) : 0.91 (6H, d, J=7Hz), 0.96 (3H, d,

J=7Hz), 1.6 - 2.1 (1H, m), 2.43 (2H,

d, J=7Hz), 2.57 (1H, wide s), 3.20 (3H, s) , 3.30 (3H, s) , 4.06 (1H, q, J=7Hz), 7, 08 (2H, d, J=9Hz), 7.33 (2H, d, J=9Hz).

For C,CHL .0,:

15 24 3

Calculated: C, 71.39; H, 9.59%.

Found: C, 71.39; H, 9.48%.

EXAMPLE 4

26.84 g of isobutylbenzene and 29.34 g of aluminum chloride were stirred under ice-cooling in 20 ml of carbon disulfide. Until the mixture became

added drop by drop over 30 min. 40.63 g of α-chloropropionyl chloride and the mixture was stirred under ice cooling for 1.5 h. It was stirred for a further 30 min. at room temperature. The reaction mixture was poured into 200 ml of ice water and 100 ml of concentrated hydrochloric acid was added. The mixture was extracted with 100 ml of diethyl ether 4 times. The extract was washed with 100 ml of water and then 4 times with 50 ml of saturated aqueous solution of sodium hydrogen carbonate, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The oily residue was dissolved in 40 ml of methanol at an elevated temperature, treated with activated charcoal and cooled to -40°C. The precipitated crystals were collected by filtration, washed with cooled methanol to give 17.83 g of α-chloro-p-isobutylpropiophenone as colorless crystals with a melting point of 51 at 53°C.

Yield: 40%

IR(KBr): 2950, 1690, 1608, 1419, 1357, 1266, 1180,

956, 861 cm"<1.>

NMR (CDCl 3 ): <$0.91 (6H, d, J=7Hz), 1.71 (3H, d,

J=7Hz), 1.5 - 2.2 (1H, m),

2.52 (2H, d, J=7Hz), 5.20 (1H, q, J=7Hz), 7.23 (2H, d, J=9Hz), 7.91 (2H, d, J=9Hz ).

For C13H170C1:

Calcd: C, 69.47; H, 7.63; Cl, 15.78%. Found: C, 69.56; H, 7.44; Cl, 15.76%.

EXAMPLE 5

Sodium methoxide (0.979 g) was dissolved in 10 mL of anhydrous methanol and the solution was stirred at room temperature under an argon atmosphere. The solution was added dropwise over 20 min. 10 ml of an anhydrous methanol solution of 2.036 g of a-chloro-p-isobutylpropiophenone and the mixture was further stirred at room temperature for 4 h. Usual work-up as in example 4 gave 2.158 g (yield 95%) of a-hydroxy-p-isobutylpropiophenone-dimethyl acetal as a pale yellow oil. Yield 95%.

EXAMPLE 6

By a method similar to that in example 1, α-(p-toluenesulfonyloxy)-p-isobutylpropiophenone-dimethylacetal was prepared as colorless crystals from α-hydroxy-p-isobutylpropiophenone-dimethylacetal.

Yield: 89%•

Mp.: 64 - 65°C (from hexane)

IR (KBr): 2960, 1360, 1185, 1090, 1050, 930, 915,

780 cm<1.>

NMR (CDCl 3 ): SO.88 (6H, d, J=7Hz), 1.09 (3H, d,

J=7Hz), 1.5 - 2.1 (1H, m), 2.40 (3H,s), 2.42 (2H, d, J=7Hz), 3.07 (3H, s), 3 .15 (3H, s), 4.93 (1H, q, J=7Hz),

6.9 - 7.4 (6H, m), 7.72 (2H, d, J=9Hz).

For C22H30°5<S:>

Calculated: C, 64.99; H, 7.44; S, 7.89%.

Found: C, 64.78; H, 7.26; S, 7.93%.

EXAMPLE T

Methanesulfonyl chloride (2.94 g) was dissolved in 5 ml of anhydrous pyridine and the solution was stirred under ice cooling. The solution was added drop by drop over 15 min. 10 ml of an anhydrous pyridine solution of 3.23 g of α-hydroxy-p-isobutylpropio-phenone-dimethyl acetal. The mixture was stirred under ice cooling for 1 h and at room temperature for 30 min. Water (30 mL) was added and the mixture was stirred for 1 h. The mixture was extracted with 10 mL of methylene chloride 3 times. The extract was washed with 10 ml of water 3 times, dried over anhydrous magnesium sulfate, and; concentrated in the presence of a small quantity of anhydrous potassium carbonate. The oily residue was purified by column chromatography (Florisil; methylene chloride) to give 3.347 g of α-(methanesulfonyloxy)-p-isobutyl-propiophenone-dimethyl acetal as a colorless oil.

Yield: 79%

IR (pure): 2960, 1350, 1175, 1095, 1065, 1040,

915 cm"<1>.

NMR (CDCl 3 ): S0'88 (6H, d, J=7Hz), 1.16 (3H, d,

J=7Hz), 1.6 - 2.1 (1H, m), 2.44 (2H,

d, J=7Hz), 3.06 (3H, s), 3.18 (3H, s), 3.26 (3H, s), 4.95 (1H, q, J=7Hz), 7.10 (2H , d, J=8Hz), 7.32 (2H, d,

J=8Hz).

For C.cH0,0_S:

16 26 5

Calculated: C, 58.16; H, 7.93; S, 9.69%.

Found: C, 58.06; H, 7.80; S, 9.60%.

EXAMPLE 8

Sodium methoxide (9.20 g) was slurried in 10 ml of anhydrous diethyl ether, and in an atmosphere of argon the solution was stirred under ice cooling. To the solution. was added drop by drop over 40 min. 80 ml of an anhydrous diethyl ether solution of 15.0 g of α-bromo-p-methoxypropiophenone. After the addition, the insoluble part was separated by filtration in a stream of argon. The filtrate was concentrated under reduced pressure to give 7.88 g of 1-(4-methoxyphenyl)-1-methoxy-1,2-epoxypropane as a light pink oil.

Yield: 68%

NMR (CDCl 3 ): «S1.00 (3H, d, J=6Hz) , 3.23 (3H, s) ,

3.52 (1H, q, J=6Hz), 3.82 (3H, s), 6.92 (2H, d, J=7Hz), 7.38 (2H, d, J=7Hz).

EXAMPLE 9

7.88 g of 1-(4-methoxyphenyl)-1-methoxy-1,2-epoxypropane and 200 mg of sodium methoxide were stirred in 30 ml of anhydrous methanol at room temperature for 15 h. Water (50 ml) was added to the reaction solution and the mixture was extracted with 20 ml of diethyl ether 3 times. The extracts were dried over anhydrous magnesium sulfate and anhydrous potassium carbonate, and concentrated under reduced pressure in the presence of a small amount of anhydrous potassium carbonate to give 8.26 g of α-hydroxy-p-methoxypropiophenone dimethyl acetal as a colorless oil. For elemental analysis, this product was purified by column chromatography (Florisil; methylene chloride).

Yield: 61%

IR (pure): 3520, 1050 cm"<1>.

NMR (CDCl 3 ): *0.94 (3H, d, J=7Hz), 2.35 (1H, d,

J=4Hz), 3.20 (3H, s), 3.33 (3H, s), 3.78 (3H, s), 4.05 (1H, dq, J=4 and 7Hz), 6.18 (2H, d, J=9Hz), 7.35 (2H,

d, J=9Hz).

For<C>12<H>18°4<:>

Calculated: C, 63.70; H, 8.02%.

Found: C, 63.98; H, 8.08%.

EXAMPLE 10

2.67 g of p-toluenesulfonyl chloride was dissolved in 5 ml of anhydrous pyridine and the solution was stirred at room temperature. To the solution was added dropwise over 10 min. 5 ml of an anhydrous pyridine solution of 1.58 g of α-hydroxy-p-methoxypropiophenone-dimethyl acetal. The mixture was stirred for 72 h. Ice water (about 20 g) was added and the mixture was extracted with 20 ml of diethyl ether 3 times. The extracts were washed with 20 ml of water, dried over anhydrous magnesium sulfate and concentrated under reduced pressure in the presence of a small amount of anhydrous potassium carbonate to give 2.12 g of α-(p-toluenesulfonyloxy)-p-methoxy-propiophenone-dimethyl acetal as a pale yellow oil.

Yield: 80%

IR (pure): 1600, 1510, 1350, 1245, 1170, 1090, 1055,

1035, 905 cm"<1.>

NMR (CDCl 3 ): til.07 (3H, d, J=7Hz), 2.40 (3H, s) ,

3.07 (3H, s), 3.12 (3H, s),

3.75 (3H, s), 4.92 (1H, q, J=7Hz),

6.7 - 7.0 (2H, m), 7.1 - 7.4 (4H, m), 7.73 (2H, d, J=8Hz).

EXAMPLE 11

By a method similar to that in example 2, α-bromo-p-(tert-butyl)isovalerophenone was prepared as a colorless liquid from p-(tert-butyl)isovalerophenone.

Yield: 72%

Kp.: 128 - 140°C/1 torr.

IR (pure): 2960, 1680, 1600 cm"<1>

NMR (CDCl 3 ) : 1.00 (3H, d, J=7Hz), 1.20 (3H, d,

J=7Hz), 1.35 (9H, s), 2.2 - 2.7 (1H, m) , 4.90 (1H, d, J=9Hz) , 7.47 (2H, d, J= 10Hz), 7.90 (2H, d, J=10Hz).

For<C>15<H>21<O>Br

Calculated: C, 60.61; II, 7,12; Br, 26.89%. Found: C, 60.71; H, 7.11; Br, 26.58%.

EXAMPLE 12

Sodium methoxide (1.62 g) was dissolved in 20 mL of anhydrous methanol, and the solution was stirred at room temperature under an atmosphere of argon. To the resulting solution was added 20 ml of an anhydrous methanol solution of 2.64 g of α-bromo-p-(tert-butyl)isovalerophenone over 15 min. and the mixture was stirred at room temperature for 18 h.

Usual work-up as in Example 3 gave 2.44 g of α-hydroxy-p-(tert-butyl)isovalerophenone-dimethyl acetal as a pale yellow oil.

Yield: 98%

IR (pure): 2950, 1110, 1040 cm<-1>.

NMR (CDCl 3 ): <$0.70 (3H, d, J=7Hz) , 0.90 (3H, d,

J=7Hz), 1.32 (9H, s), 1.0 - 1.6 (1H, m) , 2.45 (1H, wide s) , 3.22 (3H, s) , 3.25 ( 3H, s), 3.67 (1H, d, J=6Hz), 7.33 (4H, s).

EXAMPLE 13

Methanesulfonyl chloride (1.90 g) was dissolved in 14 ml of anhydrous pyridine, and the solution was stirred at room temperature, and to the solution was added dropwise over 10 min. 5 ml of an anhydrous pyridine solution of 2.34 g of α-hydroxy-p-(tert-butyl)isovalerophenone-dimethyl acetal. The mixture was stirred at this temperature for a further 24 h. Usual work-up and separation as in Example 7 gave 1.63 g of α-(methanesulfonyl-oxy)-p-(tert-butyl)isovalerof enone-dimethyl acetal as a colorless oil ( on standing at room temperature this compound crystallized).

Yield: 55%

Melting point: 80 - 86°C

IR (pure): 2960, 1357, 1176, 1060, 955 cm"<1>

NMR (CDCl 3 ): 60.70 (3H, d, J=7Hz), 0.90 (3H, d,

J=7Hz), 1.32 (9H, s), 1.4 - 1.9 (1H, m) , 3.17 (3H, s) , 3.20 (3H, s), 3.26

(3H, s) , 4.76 (111, d, J=4Hz), 7.37

(4H, p) .

For<C>18H30°5<S:>

Calculated: C, 60.30; H, 8.44; S, 8.95%

Found: C, 60.07; H, 8.23; S, 9.07%

EXAMPLE 14

Benzene (100 ml) was added to a mixture of 7.12 g of α-acetoxyacetophenone, 7.44 g of ethylene glycol and 0.200 g of p-toluenesulfonic acid monohydrate, and the mixture was heated under reflux. Formed water was removed using a "Dean-Stark" device attached to the reactor. After boiling under reflux for 21 h, 4.00 g of ethylene glycol was added. The mixture was further heated under reflux for 6 h. The water formed was distilled from. After cooling, 30 ml

of a saturated aqueous solution of sodium bicarbonate and 20 ml of water were gradually added and the mixture was extracted with 30 ml of diethyl ether 2 times. The extracts were washed with 10 ml of water, dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give 7.874 g of a residue. The residue was determined by NMR and GLC to be a mixture of α-acetoxyacetophenone-ethylene acetal and α-hydroxyacetophenone-ethylene acetal. The mixture was dissolved in 20 ml of methanol and 0.300 g of potassium carbonate was added. Water (200 mL) was added and the precipitated colorless crystals were collected by filtration and dried overnight in vacuo over potassium hydroxide: to give 4.79 g of α-hydroxyacetophenone ethylene acetal.

Dividend; 67%

NMR (CDCl 3 ): <S 2.10 (1H, broad s), 3.70 (2H, broad s) ,

3.7 - 4.0 (2H, m), 4.0 - 4.2 (2H, m), 7.2 - 7.6 (5H, m).

EXAMPLE 15

Pyridine (5 ml was added to 0.900 g of α-hydroxyacetophenone-ethylene acetal and the mixture was stirred under ice-cooling. To the mixture was added 1.08 g of p-toluenesulfonyl chloride and the mixture was stirred for 2 h under ice-cooling and then for 1 h at room temperature. The reaction mixture was again cooled with ice. Water (10 ml) was added and the mixture was stirred for 1 h and extracted with 20 ml of diethyl ether 3 times. The extracts were washed with 10 ml water 2 times, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to

yield 1.584 g of a crystalline residue. The residue was washed with a small amount of hexane to give 1.330 g of α-(p-toluenesulfonyloxy)acetophenone-ethylene acetal as colorless crystals.

Yield: 80%

NMR (CDCl 3 ): <J 2.40 (3H, s) , 3.7 - 3.9 (2H, m) ,

3.9 - 4.1 (2H, m), 4.11 (2H, s),

7.1 - 7.5 (5H, m), 7.55 (2H, d,

J=8Hz).

EXAMPLE 16

By a method similar to that according to example 15, α-(p-bromobenzenesulfonyloxy)acetophenone-ethylene acetal was produced

presented as colorless crystals from α-hydroxy-acetophenone-ethylene acetal.

Yield: 86%

NMR (CDCl 3 ): <S 3.7 - 3.9 (2H, m), 3.9 - 4.1 (2H, m),

4.16 (2H, s), 7.2 - 7.5 (5H, m), 7.63

(4H, p).

EXAMPLE 17

Sodium metal (0.46 g) was dissolved in 10 ml anhydrous

methanol, and the solution was stirred at room temperature. To the solution was added dropwise over 10 min. 10 ml of an anhydrous methanol solution of 2.19 g of 1-(2-thienyl)-2-bromo-1-propanone and the mixture was stirred for a further 3.5 h at room temperature. Normal processing as in example 3 gave 1,900

g 1-(2-thienyl)-2-hydroxy-1-propanone-dimethyl acetal as a colorless oil.

Yield: 94%

IR (pure): 3450, 1110, 1055, 980, 855, 710 cm"<1.>

NMR (CDCl 3 ) : <$" 1.05 (3H, d, J=7Hz), 2.54 (1H, broad s) ,

3.26 (3H, s), 3.30 (3H, s), 4.16 (1H,

wide q, J=7Hz), 6.9 - 7.2 (2H, m),

7.2 - 7.4 (1H, m).

EXAMPLE 18

0.606 g of 1-(2-thienyl)-2-hydroxy-1-propanone-dimethyl acetal was dissolved in 5 ml of pyridine and the solution was stirred under ice-cooling. The solution was added over 1 min. 0.30 ml of methanesulfonyl chloride and the mixture was stirred for 5 min. under ice-cooling and then 5 h at room temperature. Water (30 ml) was added and the mixture was stirred for 30 min. at room temperature and extracted with 30 ml of diethyl ether 3 times. The extracts were washed with 10 ml of water 2 times, dried over anhydrous magnesium sulfate and anhydrous potassium carbonate and concentrated under reduced pressure. The residue was purified by column chromatography (Florisil, methylene chloride) to give 0.788 g of 1-(2-thienyl)-2-(methanesulfonyloxy)-1-propanone-dimethyl acetal as a colorless oil.

Yield: 94%

IR (pure): 1360, 1180, 1120, 1055, 990, 975, 930,

905, 855, 810, 715, 540, 525 cm"<1>.

NMR (CDCl ) : <S 1.27 (3H, d,J=7Hz), 3.09 (3H, s) ,

3.27 (6H, s), 5.02 (1H, q, J=7Hz),

6.9 - 7.1 (2H, m), 7.2 - 7.4 (1H, m).

For<C>10<H>16°5<S>2<:>

Calculated: C, 42.84; H, 5.75; S, 22.87% Found: C, 42.64; H, 5.64; S, 22.90%

EXAMPLE 19

Benzenesulfonyl chloride (2.01 g) was dissolved in 10 ml of anhydrous pyridine and the solution was stirred at room temperature. 10 ml of an anhydrous pyridine solution of 1.93 g of α-hydroxy-p-isobutylpropiophenone-dimethyl acetal was added dropwise over 15 ml to the solution, and the mixture was stirred for 72 h. In a similar work-up as in example 1 2.62 g of α-(benzenesulfonyloxy)-p-isobutylpropiophenone-dimethylacetal were obtained as colorless crystals.

Yield: 88%

M.p.: 79 - 82°C

IR: (KBr): 2950, 1362, 1195, 1097, 1043, 990, 921,

813, 594 cm"<1.>

NMR (CDC13,J i & 0.86 (6H, d, J=7Hz), 1.08 (3H, d,

J=7Hz), 1.6 - 2.1 (1H, m), 2.41 (2H, d, J=7Hz), 3.02 (3H, s), 3.10 (3H, s), 4 .94 (1H, q, J=7Hz), 7.04 (2H, d, J=9Hz), 7.19 (2H, d, J=9Hz), 7.36 - 7.70 (3H, m) , 7.84 - 8.02 (2H, m).

EXAMPLE 20

1.91 g of p-toluenesulfonyl chloride was dissolved in 10 ml of anhydrous pyridine and the solution was stirred at room temperature. To the solution was added dropwise over 10 min. 10 ml of an anhydrous pyridine solution of 1.13 g of α-hydroxypropiophenone-diethyl acetal and the mixture was stirred for 72 h. Usual work-up and purification by column chromatography (Florisil, methylene chloride) gave 1.16 g of α-(p-toluenesulfonyloxy)-propiophen- on-diethyl acetal as a colorless oil.

Yield: 85%.

IR (pure): 2980, 1360, 1192, 1178, 1087, 1055, 1042,

920 cm"<1.>

NMR (CDCl 3 ) : <S 0.8 - 1.3 (9H, m) , 2.38 (3H, s) ,

3.1 - 3.6 (4H, m) 4.89 (1H, q, J=7Hz) , 7.1 - 7.5 (7H, m), 7.80 (2H, d, J=9Hz) .

For C20H26°5<S>

Calcd: C, 63.46; H, 6.93; S, 8.47%

Found: C, 63.54; H, 6.90; S, 8.35%

EXAMPLE 21

0.526 g of α-(p-toluenesulfonyloxy)propiophenone dimethyl acetal and 0.150 g of calcium carbonate were heated under reflux for 72 h in 10 ml of a mixture of water and methanol (3:7 by weight). Water (10 mL) was added and the mixture was extracted with

10 ml of diethyl ether 3 times. The extracts were washed with 10

ml of water and dried over anhydrous magnesium sulfate. The product was quantitatively analyzed by gas chromatography (internal standard method) and found to contain 0.162 g of methyl-α-phenylpropionate. Yield 66%.

EXAMPLE 2 2

1.75 g of α-(p-toluenesulfonyloxy)propiophenone-dimethyl acetal and

0.500 g of calcium carbonate was heated under reflux for 72 h in 33 ml of a mixture of water and methanol (3:7 by weight). Water (50 ml) was added and the mixture was extracted with 30 ml of diethyl ether 3 times. The extracts were washed with 30 ml of water and concentrated under reduced pressure to approx. 5 ml. Methanol (12 ml), 5 ml of water and 7 ml of a 10% aqueous solution of potassium hydroxide were added to the residue,

and the mixture was heated under reflux for 5 h. Water (30 mL) was added and the mixture was washed with 20 mL of diethyl ether 5 times. The aqueous layer was adjusted to pH 1 with concentrated hydrochloric acid and extracted with 20 ml of diethyl ether 4 times. The extracts were washed with 20 ml of water, dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give 0.358 g of α-phenylpropionic acid as a color- loose oil. Yield 48%. This product fully corresponded to an authentic sample in IR and NMR spectral data.

EXAMPLES 23 TO 3 5

0.526 g of α-(p-toluenesulfonyloxy)propiophenone-dimethyl acetal and an equimolar amount of each of the different bases shown in Table 1 were heated on an oil bath in 10 ml of each of the different solutions shown in Table 1. Water (10 ml) was added, and the mixture was extracted with 10 ml of diethyl ether 3 times. The extracts were washed with 10 ml of water and dried over anhydrous magnesium sulfate.

The product was analyzed for methyl-α-phenylpropionate by gas chromatography in the same way as in Example 21.

The results are shown in table 1.

EXAMPLE 3' 6

0.410 g of α-(p-toluenesulfonyloxy)-p-isobutylpropiophenone-dimethyl acetal and 0.100 g of calcium carbonate were heated under reflux in a mixture of water and methanol (3:7 by weight)

for 22 h. Water (15 mL) was added and the mixture was extracted with 10 mL of diethyl ether 3 times. The extracts were washed with 10 ml of water, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The oily one

residue was purified by column chromatography (silica gel, methylene chloride) to give 0.180 g of methyl α-(4-isobutylphenyl)propionate as a colorless oil. Yield 81%. This product fully corresponded to an authentic sample in IR and NMR spectral data.

EXAMPLE 37

0.910 g of α-(p-toluenesulfonyloxy)<l->p-isobutylpropiophenone-dimethyl acetal and 1.25 g of potassium carbonate were heated for 20 h under reflux in 26 ml of a mixture of water and methanol (3:7 by weight, water ( 30 ml) was added and the mixture was washed with 10 ml of methylene chloride 4 times. The aqueous layer was adjusted to pH 2 with dilute hydrochloric acid and extracted with 20 ml of methylene chloride 4 times. The extracts were washed with 30 ml of water, dried over anhydrous magnesium sulfate to to give 0.335 g of α-(4-isobutylphenyl)propionic acid as colorless crystals with a melting point of 71 to 75°C. Yield 73%. This product fully corresponded to an authentic sample in

IR and NMR spectral data.

EXAMPLE 38

0.991 g of α-(methanesulfonyloxy)-p-isobutylpropiophenone-dimethyl acetal and 0.300 g of calcium carbonate were heated under reflux for 72 h in 10 ml of a mixture of water and methanol (3:7 by weight). Usual work-up followed by alkaline hydrolysis of the crude product which in Example 22 gave 0.519 g of α-(-4-isobutylphenyl)propionic acid as phaseless crystals with a melting point of 73 to 75°C. Yield 84%. This product fully corresponded to an authentic sample in IR and NMR spectral data.

EXAMPLE 3 9

2.12 g of α-(p-toluenesulfonyloxy)-p-<m>ethoxy-propiophenone-diraethyl acetal and 0.560 g of calcium carbonate were heated under reflux for 13 h in 20 ml of a mixture of water and methanol (3:7 by weight) . Usual work-up followed by hydrolysis of the crude product which in Example 22 gave 0.714 g of α-(4-methoxyphenyl)propionic acid as pale yellow crystals with a melting point of 47 to 50°C. Yield 57%.

EXAMPLE 4 0

0.735 g of α-(methanesulfonyloxy)-p-(tert-butyl)isovalerophenone dimethyl acetal and 0.200 g of calcium carbonate were heated under reflux for 72 h in 10 ml of a mixture of water and

methanol (3:7 by weight). Usual work-up as in Example 36 and purification by column chromatography (silica gel, methylene chloride) to give methyl α-[4-(tert-butyl)phenyl]isovalerate as a colorless oil.

IR (pure):

2965, 1745, 1165, 1025 cm"<1.>

NMR (CDCl 3 ):

0.71 (3H, d, J=7Hz), 1.02 (3H, d, J=7Hz), 1.32 (9H, s), 2.1 - 2.6 (1H, m), 3, 10 (1H, d, J=11Hz), 3.60 (3H, s), 7.1 - 7.4 (4H, m).

For C16H2402:

Calculated: C, 77.37; H, 9.74%

Found: C, 77.26; H, 9.62%

EXAMPLE 41

0.668 g of α-(p-toluenesulfonyloxy)acetophenone-ethylene acetal was dissolved in 8 ml of 1,3-dimethyl-2-imidazolidinone (DMI), and 200 mg of calcium carbonate and 0.2 ml of water were added. The mixture was heated at 180°C for 22 h with stirring. After

cooling, 30 ml of water was added and the mixture was extracted with 20 ml of diethyl ether 3 times. The extracts were washed with 10 ml of water 2 times and dried over anhydrous magnesium sulfate. The aqueous layers were combined and 4 ml of concentrated hydrochloric acid was added. The mixture was extracted with 20 ml of diethyl ester 3 times. The extracts were washed with 10 ml

water twice and dried over anhydrous magnesium sulfate.

The residues that remained after concentration under reduced pressure and the extracts obtained in neutral or acid condition was combined and 400 ml of potassium hydroxide was added. The mixture was heated under reflux for 16 h in a mixture of 6 ml of methanol and 2 ml of water. After cooling, 30 ml of water was added and the mixture was washed with 20 ml of diethyl ether 3 times. The aqueous layer was acidified to a pH of approx. 2 by adding approx. 7 ml of 3.5% hydrochloric acid and extracted with 20 ml of diethyl ether 3 times. The extracts were washed with 10 ml of water, dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give 92 mg of a residue. This residue was found to be a mixture of benzoic acid and phenylacetic acid by its NMR and GLC of its methyl ester obtained by treatment with diazomethane. NMR spectral data showed that it contained 65 mg (yield 27%) of benzoic acid and 27 mg (yield 10%) of phenylacetic acid.

EXAMPLE 4 2

0.798 g of α-(p-bromobenzenesulfonyloxy)acetophenoneethylene acetal was dissolved in 8 ml of DMI and 200 mg of calcium carbonate and 0.5 ml of water were added. The mixture was heated at 160°C for 18

h while stirring. In the same manner as in Example 41, the reaction mixture was worked up and the crude product was subjected to alkaline hydrolysis to give 84 mg of a semi-solid.

The semi-solid substance was found by NMR to be a mixture of benzoic acid and phenylacetic acid (7.0:4.5 per mol). Accordingly, the mixture was determined to contain 49 mg (yield 20%) of benzoic acid and 35 mg (yield 13%) of phenylacetic acid.

EXAMPLE 4 3

0.560 g of 1-(2-thienyl)-2-(methanesulfonyloxy)-1-propanone-dimethyl acetal and 0.200 g of calcium carbonate were heated under reflux for 42 h in a mixture of water and methanol (3:7 by weight). Water (30 mL) was added and the mixture was extracted with 30 mL of diethyl ether 3 times. The extracts were washed with 10 ml of water 2 times, dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give 316 mg of methyl-α-(2-thienyl)propionate as a colorless oil. This product fully corresponded to an authentic sample in IR and NMR

spectral data. Yield 93% (in crude form).

The crude oil was subjected to simple distillation at 130°C (bath temperature) and 17 torr to give 279 mg of pure product. Yield 82% (after purification).

The aqueous layers obtained by extraction were combined and

6 ml of concentrated hydrochloric acid was added. The mixture was extracted with 15 ml of diethyl ether 3 times. The extracts were washed twice with 10 ml of water, dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give 20

mg α-(2-thienyl)-propionic acid as a colorless oil. Dividend 6%. This product fully corresponded to an authentic sample in IR and NMR spectral data.

EXAMPLE 4 4

0.565 g of 1-(2-thienyl)-2-methanesulfonyloxy)-1-propanone-dimethyl acetal and 0.202 g of calcium carbonate were heated under reflux for 21 h in 6 ml of a mixture of water and methanol

(3:7 per weight). To the reaction mixture was added 0.420 g of sodium hydroxide and the mixture was stirred at room temperature for 15 h and then heated under reflux for 2 h. Water (30 ml) was added and the mixture was washed with 20 ml of diethyl ether. Concentrated hydrochloric acid (4 ml) was added to the aqueous layer and the mixture was extracted with 20 ml of diethyl ether 3 times. The extracts were washed with 10 ml of water,

dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give 0.299 g of α-(2-thienyl)propionic acid as a colorless oil. Yield 95%.

EXAMPLE 4 5

Sodium hydroxide (0.420 g) was dissolved in 6 ml of a mixture of water and methanol (3:7 by weight) and 0.574 g of 1-(2-thienyl)-2-(methanesulfonyloxy)-1-propanone-dimethyl acetal was added. The mixture was heated under reflux for 21 h. Water (40 mL) was added and the mixture was washed with 20 mL of diethyl ether. Concentrated hydrochloric acid (3 ml) was added to the aqueous layer and the mixture was extracted with 20 ml diethyl ether 3 times. The extracts were washed with 5 ml of water, dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give 0.291 g of α-(2-thienyl)propionic acid as a colorless oil. Yield 91%.

EXAMPLE 4 6

0.674 g of 1-(2-thienyl)-2-(p-toluenesulfonyloxy)-1-propanone dimethyl acetal and 0.200 g of calcium carbonate were heated under reflux for 12 hours in 10 ml of a mixture of water and methanol (3:7 by weight ). Usual work-up as in Example 36 gave an oily crude product which was subjected to simple distillation at 110-120°C (bath temperature) and 17 torr and gave 0.253 g of methyl-α-(2-thienyl)-propionate as a colorless oil. Yield 79.%.

EXAMPLE 4 7

0.684 g of 1-(2-thienyl)-2-(benzenesulfonyloxy)-1-propanone dimethyl acetal and 0.200 g of calcium carbonate were heated under reflux for 8 hours in 10 ml of a mixture of water and methanol (3:7 by weight). Conventional work-up as in Example 36 gave an oily crude product, which was subjected to simple distillation at 110°C (bath temperature) and 15 torr and gave 0.277 g of methyl-α-(2-thienyl)propionate as a colorless oil. Yield 81%.

EXAMPLE 48

0.299 g of α-(methanesulfonyloxy)-p-acetyl-aminopropiophenone-dimethyl acetal and 0.090 g of calcium carbonate were heated under reflux for 21 hours in 3 ml of a mixture of water and methanol (3:7 by weight). Water (Z0 ml) was added and the mixture was extracted with 20 ml of methylene chloride three times. The extracts were washed with 10 ml of water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to give a crystalline residue. The residue was purified on column chromatography (silica gel, methylene chloride-diethyl ether)

and gave 0.186 g of methyl-α-(4-acetylaminophenyl)propionate as colorless crystals.

Yield: 93%

Mp.:.- 107 - 1Q9°C (from ethanol-hexane)

IR (KBr) :

1740, 1665, 1610, 1555, 1515, 1415, 1330, 1160 860, 840 cm"<1>.

NMR (CDCl 3 ):

§1.46 (3H, d, J=7Hz), 2.11 (3H, s), 3.64 (3H, s),

3.67 (1H, q, J=7Hz), 7.17 (2H, d, J= 8Hz), 7.53 (2H, d, J=8Hz), 8.17 (1H, broad).

For<C>12<H>15N03:

Calculated: C 65.14; H, 6.83; N, 6.33%

Found: C 64.94; H, 7.00; N, 6.27%

EXAMPLE 49

0.329 g of α-(benzenesulfonyloxy)-p-isobutylpropiophenone dimethyl acetal and 0.10 g of calcium carbonate were heated under reflux for 10 hours in 10 ml of a mixture of water and methanol (3:7 by weight). Similar work-up as in Example 48 and purification by column chromatography (silica gel, methylene chloride) gave 0.181 g of methyl-a-(4-isobutylphenyl) propionate as a colorless oil. Yield 82%.

EXAMPLE 50

0.392 g of α-(benzenesulfonyloxy)-p-isobutylpropiophenonedimethyl acetal was heated in 4 ml of a mixture of water and pyridine (1:3 by weight) over an oil bath at 100°C for 19 hours. Similar work-up as in Example 48 and purification by column chromatography (silica gel, methylene chloride) gave 0.164 g of methyl-α-(4-isobutylphenyl)propionate as a colorless oil. Yield 74%.

EXAMPLE 51

0.392 g of α-(benzenesulfonyloxy)-p-isobutylpropiophenonedimethyl acetal was mixed with 10 ml of a mixture of water and methanol (3:7 by weight) and 2 ml of a 10% aqueous solution of potassium hydroxide, and the mixture was heated under reflux for 9 hours. Water (30 mL) was added and the mixture was washed with 15 mL of methylene chloride four times. The aqueous layer was adjusted to a pH of less

than 1 with concentrated hydrochloric acid, and extracted with 15 ml of methylene chloride four times. The extracts were dried over anhydrous magnesium sulfate and concentrated under reduced pressure

and gave 0.138 g of α-(4-Isobutylphenyl)propionic acid as colorless crystals with a melting point of 73 to 75°C. Yield 67%.

EXAMPLE 52

0.150 g of α-(p-toluenesulfonyloxy)propiophenone diethyl acetal and 0.05 g of calcium carbonate were heated under reflux for 72 hours in 10 ml of a mixture of water and methanol (3:7 by weight). Water (20 mL) was added, and the mixture was extracted with 5 mL of diethyl ether four times, and dried over anhydrous magnesium sulfate. The product was quantitatively analyzed by gas chromatography (internal standard method) and found to contain 23 mg of ethyl-a-phenylpropionate. Yield 32%.

EXAMPLE 5 3

0.978 g of α-(methanesulfonyloxy)-p-fluoropropiophenonedimethyl acetal and 0.33 g of calcium carbonate were heated under reflux for 24 hours in 15 ml of a mixture of water and methanol (3:7 by weight). By the same work-up and purification as in Example 49, 0.454 g of methyl-α-(4-fluoro-phenyl)propionate was obtained as a colorless oil. Yield 76%.

IR (pure):

1744, 1607, 1513, 1460, 1439, 1340, 1230, 1210, 1170, 1160, 840, 796 cm"<1>.

NMR (CDCl 3 ):

1.46 (3H, d, J=7Hz), 3.60 (3H, s), 3.67 (1H,

q, J=7Hz) , 6 , 8-7.4 (4H, m) .

EXAMPLE 54

0.490 g of 1-(6-methoxy-2-naphthyl)-2-methane-sulfonyloxy)-1-propanone dimethyl acetal and 0.140 g of calcium carbonate were heated under reflux for 5 hours in 10 ml of a mixture of water and dimethylformamide (1:- after weight). Water (20 mL) was added and the mixture was extracted with 7 mL of methylene chloride four times. The extracts were washed with 10 ml of water four times, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by column chromatography (silica gel, methylene chloride) and

gave 0.323 g of methyl-α-(6-methoxy-2-naphthyl)propionate as colorless crystals with a melting point of 65-68°C. Yield 94%. The product fully corresponded to an authentic sample in IR and NMR spectral data.

EXAMPLE 55<1>

0.354 g of 1-(6-methoxy-2-naphthyl)-2-methanesulfonyloxy-1-propanonedimethyl acetal and 0.10 g of calcium carbonate were heated under reflux for 28 h in 8 ml of a mixture of water and ethanol (3:7 by weight). Water (20 mL) was added and the mixture was extracted with 10 mL of methylene chloride three times. The extracts were washed with 20 ml of water, dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give 0.178 g of methyl-α-(6-methoxy-2-naphthyl)propionate as colorless crystals. Yield 73%.

EXAMPLE 56

One of two possible diastereomers of 1-(6-methoxy-2-naphthyl)-2-(d-10-camphorsulfonyloxy)-1-propanone dimethyl acetal was obtained (m.p. 102-105°C; ta]" + 32.5° (c=1, chloroform) ). 170 mg of this diastereomer and 40 mg of calcium carbonate were heated at a bath temperature of 110°C for 14 hours in 5 ml of a mixture of water and dimethylformamide (1:4 by weight). Water ( 20 ml) was added, and the mixture was extracted with 10 ml of diethyl ether four times. The extracts were washed with 10 ml of water four times, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by column chromatography (silica gel, methylene chloride) to give 68 mg of methyl-(-)-α-(6-methoxy-2-naphthyl)propionate as colorless crystals.

Yield: 80.2%

M.p.: 94.5 - 95°C.

[a]^° : -78.2° (c=1, chloroform)

IR. (KBr): 2970, 1739, 1602, 1450, 1334, 1270, 1231,

1205, 1172, 1158, 1028, 893, 856, 823 cm"<1.>

The product was in NMR spectral data consistent with methyl α-(6-methoxy-2-naphthyl)propionate obtained in Example 54.

EXAMPLE 57

0.31 ml (0.44 g) of iodotrimethylsilane and 2 drops of cyclohexene were stirred in 5 ml of anhydrous methylene chloride at room temperature in an atmosphere of argon. To the mixture was added dropwise .4 ml of an anhydrous methylene chloride solution of 529 mg of 1-phenyl-2 -(p-toluenesulfonyloxy)-1-propanonedimethyl acetal. The mixture was stirred at room temperature for 3 hours. Then 5 ml of a saturated aqueous solution of sodium hydrogencarbonate was added. The organic layer was washed successively with 5 ml of a 10%' 1g aqueous solution of sodium thiosulfate, 5ml of water, 5ml of a 10% aqueous solution of sodium bicarbonate and 5ml of water, and dried over anhydrous magnesium sulfate. The product was analyzed quantitatively by gas chromatography (internal standard method) and found to contain 226.4 mg methyl-α-phenylpropionate Yield 91.9%.

EXAMPLES 58-62

176 mg of 1-phenyl-2-(p-toluenesulfonyloxy)-1-propanonedimethyl acetal and each of the oxygen affinity agents shown in Table 2 in the amounts indicated were stirred in 4 ml of anhydrous methylene chloride at each of the temperatures shown in Table 2. Water (5 mL) was added and the mixture was extracted with 5 mL of methylene chloride four times. The extracts were washed with 10 ml of water and dried over anhydrous magnesium sulfate.

The product was analyzed for methyl-α-phenylpropionate by gas chromatograph in the same way as in example 57. The results are shown in table 2.

EXAMPLE 6 3

3.849 g of 1-(4-chlorophenyl)-2-(p-toluenesulfonyloxy)-1-propanonedimethyl acetal was stirred at room temperature in an argon atmosphere in 10 ml of anhydrous methylene chloride. A solution obtained by dissolving 1.71 ml (2.40 g) of iodotrimethylsilane and 2 drops of cyclohexene in 2 ml of anhydrous methylene chloride was added dropwise at room temperature and the mixture was stirred for 30 minutes. The same processing as in example 57

gave an oily crude product, which was found by its NMR spectrum to contain 1.61 g of methyl-α-(p-chlorophenyl)propionate. Yield 81.0%.

EXAMPLE 6 4

0.20 ml (0.28 g) of iodotrimethylsilane and 1 drop of cyclohexene were stirred in 8 ml of anhydrous methylene chloride at room temperature under an argon atmosphere. Then, 6 ml of an anhydrous methylene chloride solution of 490 mg (1.00 mmol) of 1-(6-methoxy-2-naphthyl)-2-(d-10-camphorsulfonyloxy)-1-propanonedimethyl-acetal with a ta] ^ of 32.5° (c=1.00, chloroform) added dropwise, and the mixture was stirred at room temperature for 1 hour. 10 ml of a saturated aqueous solution of sodium bicarbonate was added. The same work-up as in Example 57 followed by purification by column chromatography (silica gel, methylene chloride) gave 230 mg of methyl (R) (-)-α-(6-methoxy-2-naphthyl)propionate as colorless crystals with a melting point of 85-92 °C. Yield 94.2%. This product was found to be optically pure by in-use NMR spectroscopy

of an optically active displacement agent Eu (TFC)3•

EXAMPLE 6 5

By a similar procedure as in Example 17, 1-(4-methoxyphenyl)-2-hydroxy-1-propanone dimethylacetate was prepared as a pale yellow oil from 1-(4-methoxyphenyl)-2-bromo-1-propanone. Without purification, the crude product was used in the reaction of Example 66.

EXAMPLE 66

By a procedure similar to example 7, 1-(4-methoxy-phenyl)-2-methanesulfonyloxy-1-propanone dimethylacetate was prepared as a pale yellow oil from 1-(4-methoxyphenyl)-2-hydroxy-1-propanone dimethyl acetal obtained in example 65 .Yield 80.1% [from 1-(4-methoxyphenyl)-2-bromo-1-propanone].

IR (pure):

2935, 1615, 1517, 1358, 1257, 1176, 1100, 1065, 145, 915 cm"<1>.

NMR (CDCl 3 ):

S 1.18 (3H, d, J=6Hz), 3.09 (3H, s), 3.21 (3H, s), 3.28 (3H, s), 3.80 (3H, s), 4.97 (1H, q, J=6Hz), 6.87 (2H, d, J=9Hz), 7.37 (2H, d, J=9Hz).

EXAMPLE 67

1.007 g (3.308 mmol) of 1-(4-methoxyphenyl)-2-methanesulfonyloxy-1-propanone dimethyl acetal and 330 mg (3.30 mmol) of calcium carbonate were refluxed with stirring for 20 hours in 10 ml of a mixture of water and methanol (3 :7 by weight). By the same work-up and purification as in Example 49, 597 mg of methyl-α-(4-methoxyphenyl)propionate was obtained as a colorless oil. Yield 92.9%.

NMR (CDCl 3 ):

£1.47 (3H, d, J=7Hz), 3.61 (3H, s), 3.67 (1H, q, J= 7Hz), 3.73 (3H, s), 6.83 (2H , d, J=9Hz), 7.19 (2H,d, J=9Hz).

EXAMPLE 68

In a manner similar to that of Example 20, 1-(2-thienyl)-2-(p-toluenesulfonyloxy)-1-propanone dimethyl acetal was prepared as a colorless oil in a yield of 64% from 1-(2-thienyl)-2- hydroxy-1-propanone dimethyl acetal.

IR (pure) :

1360, 1190, 1180, 1060, 985, 925, 905, 820, 790, 710, 665, 565cm"<1>.

NMR (CDCl 3 ):

£1.19 (3H,~ d, J=7Hz), 2.40 (3H, s), 3.08 (3II,s), 3.14 (3H, s) , 4.98 (111, q, J=7Hz), 6.94 (2H, d, J=3Hz), 7.2-7.4 (311, m) , 7.80 (2H, d, J=8Hz) .

EXAMPLE 69

In a manner similar to that of Example 20, 1-(2-thienyl)-2-benzenesulfonyloxy)-1-propanone dimethyl acetal was prepared as a colorless oil in a yield of 83% from 1-(2-thienyl)-2-hydroxy-1 -propanone dimethyl acetal and benzenesulfonyl chloride.

IR (pure):

1360, 1190, 1060, 980, 925, 900, 590, 555 cm"<1>.

NMR (CDC1'3):

£1.20 (3H, d, J=7Hz), 3.08 (3H, s), 3.14 (3H, s), 5.01 (1H, q, J=7Hz), 6.8-7 .1 (2H, m) , 7.2-7.4

(1H, m) , 7.4-7.7 (3H, m) , 7.9-8.1 (2H, m) .

EXAMPLE 70

Sodium metal (1.30 g, 56.5 mmol) was dissolved in 30 mL of anhydrous ethanol and the mixture was stirred at room temperature. 20 ml of an anhydrous ethanol solution of 5.33 g (0.025 mol) α-bromopropiophenone was added dropwise over 15 minutes to the solution, and the mixture was stirred for a further 40 minutes at room temperature. Water (100 ml) was added,

and the mixture was extracted with 60 ml of diethyl ether twice. The extracts were washed with water, dried over anhydrous magnesium sulfate and anhydrous potassium carbonate, and concentrated under reduced pressure. The residue was dissolved in 30 ml of anhydrous ethanol containing a catalytic amount of metallic sodium dissolved in it, and the solution was stirred for 2 days at room temperature. Usual work-up as in Example 3 gave 4.497 g of 1-phenyl-2-hydroxy-1-propanone diethyl acetal as a colorless oil.

Yield: 80.2%

IR (pure):

2960, 1452, 1120, 1092, 1057, 1040, 772, 709 cm"<1>.

NMR (CDCl 3 ):

0.94 (3H, d, J=6Hz), 1.05-1.40 (6H, m), 2.61 (1H, wide s), 3.22-3.83 (4H, m), 4 .05 (1H, q, J=6Hz), 7.1-7.7 (5H, m).

EXAMPLE 71

Acetanilide (3.33 g) and 4.0 mL (5.2 g) of α-chloropropionyl chloride were stirred at room temperature in 20 mL of carbon disulfide. Then 7.0 g of finely powdered aluminum chloride was added portionwise over the course of 2 minutes. The mixture was stirred at room temperature for 25 minutes and heated under reflux for 50 minutes with stirring. After cooling, the reaction mixture separated into two layers. The upper layer was removed by decantation, and the lower layer, which was black and tarry, was poured into ice water. The precipitated crystals were collected by filtration. Recrystallization from ethanol gave

. 1.860 g of 1-(4-acetylaminophenyl)-2-chloro-1-propanone as colorless crystals. The upper layer of the reaction mixture, the filtrate formed during collection of the crystals and the mother liquor for the recrystallization were combined, and extracted with 50 ml of methylene chloride three times. The extracts were washed with 50 ml of water, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. Recrystallization of the residue from ethanol gave 1.434 g of 1-(4-acetylaminophenyl)-2-chloro-1-propanone. The mother liquor was concentrated under reduced pressure, and the residue was purified by column chromatography (silica gel, methylene chloride and ether). Recrystallization from methanol gave a further 0.868 g of the above product. The total amount of product was 4.162 g, and the total yield was 75%.

Colorless crystals.

M.p.: 123-125°C (from ethanol)

IR (KBr):

1690, 1675, 1595, 1540, 1415, 1320, 1360, 1180, 965,860, 665 cm<-1>.

NMR (CDCl3):

<51.70 (3H, d, J=7Hz) , 2.18 (3H, s) , 5.18 (1H, q,

J=7Hz), 7.63 (2H, d, J=9Hz), 7.95 (2H, d, J=9Hz), 7.8-8.1 (1H, wide s).

For C1;LH12C1N02:

Calculated: C, 58.54; H, 5.36; Cl, 15.71; N , 6.21% found: C 58.59; h, 5.40; Cl, 15.63; N, 6.23%.

EXAMPLE 72

By an operation similar to that in Example 17, 1-(4-acetylamino-phenyl)-2-hydroxy-1-propanone dimethyl acetal was prepared as a glassy substance from 1-(4-acetylaminophenyl)-2-chloro-1-propanone. Without purification, the crude product was used in the reaction in Example 73.

NMR (CDCl 3 ):

2 0.95 (3H, d, J=7Hz), 2.14 (3H, s), 2.94 (1H,

wide s), 3.21 (3H, s), 3.33 (3H, s), 4.10 (1H, q, J=7Hz), 7.37 (2H, d, J=8Hz), 7, 51 (2H, d, J=8Hz), 8.93 (1H, wide s).

EXAMPLE 7 3

All of the 1-(4-acetylaminophenyl)-2-hydroxy-1-propanonedimethyl acetal obtained in Example 72 was dissolved in 5 ml of pyridine and 0.60 ml (0.89 g) of methanesulfonyl chloride was added. The mixture was stirred at room temperature for 5 hours. The reaction mixture was cooled with ice and 30 ml of water was added. The temperature was raised to room temperature, and the mixture was stirred for 10 minutes and extracted with 20 ml of ethyl acetate four times. The extracts were dried by successive addition of anhydrous sodium sulfate and anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by column chromatography ("Florisil", methylene chloride and diethyl ether) to give 1.537 g of 1-(4-acetylaminophenyl)-2-methanesulfonyloxy-1-propanonedimethylacetal as a colorless glassy solid. Yield 93% [from 1- (4-acetylaminophenyl)-2-chloro-1-propanone] .

IR (KBr):

1675, 1610, 1540, 1350, 1175, 915, 525 cm"<1>.

NMR (CDCl 3 )

S 1.14 (3H, d, J=7Hz), 2.52 (3H, s), 3.08 (3H, s), 3.18 (3H, s), 3.24 (3H, s), 4.94 (III, q, J=7Hz), 7.36 (2H, d, J=9Hz), 7.54 (2H, d, J=9Hz), 8.52

1H, wide s).

EXAMPLE 74

In the same manner as in Example 17, 1-(4-fluorophenyl)-2-hydroxy-1-propanone dimethyl acetal was prepared as a pale yellow oil from 1-(4-fluorophenyl)-2-bromo-1-propanone. Without purification, this product was used in the reactions in examples 70 and 76.

IR (pure):

2975, 2937, 1610, 1512, 1230, 1159, 1105, 1053,

982, 839 cm<-1>.

NMR' (CDCl 3 ):

£0.93 (3H, d, J=6Hz) , 2.53 (1H, wide s) , 3.23

(3H, s), 3.33 (3H, s), 4.08 (1H, wide q, J=6Hz), 6.83-7.18 (2H, m), 7.32-7.60 ( 2H, m).

EXAMPLE 75

By the same procedure as in example 7, 1-(4-fluoro-phenyl)-2-methanesulfonyloxy-1-propanone dimethyl acetal was prepared as a colorless oil from 1-(4-chlorophenyl)-2-hydroxy-1-propanone dimethyl acetal obtained in example 74. Yield 82.3% [from 1-(4-fluorophenyl)-2-bromo-1-propanone].

IR (pure):

2940, 1610, 1512, 1359, 1228, 1180, 1160, 1098, 1067, 1045, 972, 918 cm'<1>.

NMR (CDCl 3 ):

S 1.15 (3H, d, J=6Hz), 3.06 (3H, s), 3.21 (3H, s), 3.24 (3H, s), 4.96 (1H, q, J =6Hz), 6.88-7.16 (2H, m), 7.32-7.58 (2H, m).

EXAMPLE 76

In the same way as in Example 20, 1-(4-fluorophenyl)-2-(p-toluenesulfonyloxy)-1-propanone dimethyl acetal was prepared as colorless crystals with a melting point of 96 - 99°C from 1-(4-fluorophenyl)-2 -hydroxy-1-propanonedimethylacetal obtained in Example 74. Yield 76.2% [from 1-(4-fluorophenyl)-

2-bromo-l-propanone].

M.p.: 101°C (from methanol)

(KBr):

2948, 1605, 1510, 1360, 1346, 1192, 1181, 1090, 1053, 932, 918, 820, 786, 670, 561 cm"<1>.

NMR (CDCl 3 ):

<Sl.05 (3H, d, J=6Hz), 2.40 (3H, s), 3.08 ( 311, s),

3.10 (3H, s), 4.93 (lH, q, J=6Hz), 6.82-7.08

(2H, m), 7.16-7.46 (4H, m), 7.73 (2H, d, J=8Hz).

For C18<H>21<F>03S:

Calculated: C, 58.68; H, 5.75%

Found: C, 58.98; H, 5.96%.

EXAMPLE 7 7

8.57 g of 1-(6-methoxy-2-naphthyl)-1-propanone (US patent no.

2,683,738) was dissolved in 60 ml of anhydrous dioxane and the solution was stirred at room temperature. To the solution was added 13.57 g of pyridine hydrobromide perbromide, followed by stirring for a further 1 hour. 200 ml of a 3% aqueous solution of sodium bisulphite was added to the mixture and after stirring at room temperature for 3 hours the precipitated crystals were filtered, washed with water and dried in vacuo over potassium hydroxide to give 11.66 g of 1-( 6-Methoxy-2-naphthyl)-2-bromo-1-propanone with a melting point of 73-75°C as pale yellow crystals. Yield, 99%.

M.p.: 68-69°C (from benzene).

NMR (CDCl 3 ):

Sl,90 (3H, d, J=7Hz), 3.85 (3H, s), 5.36 (1H, q, J=7Hz), 6.9 - 7.3 (2H, m), 7, 5-8.1 (3H, m), 8.38 (1H, wide s) .

For C, .H, -,Br0_ :

14 13 2

Calculated: C, 57.35; H, 4.47; Br, 27.26%

Found: C, 57.27; H, 4.66; Br, 27.23%

EXAMPLE 78

By a similar procedure to that of Example 3, 1-(6-methoxy-2-naphthyl)-2-hydroxy-1-propanone dimethyl acetal was prepared as a colorless oil from 1-(6-methoxy-2-naphthyl)-2-bromo -1-propanone. Dividend, 100%. The product crystallized after being purified by column chromatography ("Florisil", methylene chloride) and allowed to stand at room temperature.

Colorless crystals.

Temp. 56-59°C.

IR (KBr):

3500, 1637, 1610, 1488, 1276, 1215, 1175, 1118, 1106, 1040, 859 cm"<1>.

NMR (CDCl 3 ):

&0.97 (3H, d, J=7Hz) , 2.48 (1H, wide s) , 3.20 (3H, s), 3.36 (3H, s), 3.82 (3H, s), 4.14 (1H, q, J=7Hz), 7.00-7.24 (2H, m), 7.40 - 7.98 (4H, m). Fo<rC>16H20<0>4<:>

Calcd: C, 69.54; H, 7.30%

Found: C, 69.25; H, 7.28%

EXAMPLE 79

By a method similar to that in Example 7, 1-(6-methoxy-2-naphthyl)-2-methanesulfonyloxy-1-propanonedimethyl acetal was prepared as a colorless oil from 1-(6-methoxy-2-naphthyl)- 2-hydroxy-1-propanone dimethyl acetal. Yield, 84%.

IR (pure):

1640, 1615, 1492, 1360, 1280, 1182, 901, 820 cm"<1>. NMR (CDCl 3 ): £ 1.19 (3H, d, J=7Hz), 3.09 (3H, s), 3 .22 (3H, s), 3.31 (3H, s), 3.87 (3H, s), 5.05 (1H, q, J=7Hz), 7.04-7.24 (2H, m ) , 7 .42-7 .94 (4H, m) .

For C. _H_o0,S:

17 22 6

Calculated: C, 57.61; 11, 6.26; S, 9.05%

Found: C, 57.21; H, 6.02; S, 8.85%.

EXAMPLE 80

350 mg of sodium metal was dissolved in 40 ml of anhydrous methanol and the solution was stirred at room temperature. 2.93 g of 1-(6-methoxy-2-naphthyl)-2-bromo-1-propanone was added to the solution, followed by stirring for 24 hours. 50 mL of water was added to the mixture which was then extracted with methylene chloride (15 mL x 4). The extract was dried over anhydrous magnesium sulfate and anhydrous potassium carbonate and concentrated below

reduced pressure and qa 2.84 5 g of a crude product of 1-(6-methoxy-2-naphthyl)-2-hydroxy-1-propanonedimethyl acetal. 1.11 g of the crude product was dissolved in 3 ml of anhydrous pyridine, followed by stirring at room temperature. 993 mg of d-10-camphor sulfonyl chloride was added to the solution and the mixture was stirred for 40 minutes. 20 mL of water was added to the mixture which was then extracted with methylene chloride (10 mL x 3). The extract was dried by successively adding anhydrous magnesium sulfate and anhydrous potassium carbonate to the extract and concentrated under reduced pressure. The remaining oil was purified by column chromatography ("Florisil", methylene chloride) to give 1.467 g of 1-(6-methoxy-2-naphthyl)-2-(d-10-camphorsulfonyloxy)-1-propanonedimethyl acetal as a colorless glassy substance . Yield 76.8% [from 1-(6-methoxy-2-naphthyl)-2-bromo-1-propanone]. The product was found to be a 1:1 mixture of two diastereomers by high performance liquid chromatography and NMR spectrum.

1,067 g of the product thus obtained was dissolved in 4 ml of methanol and the solution was allowed to stand for 2 days at 2-4°C

and gave 355 mg of colorless crystals with a melting point of 90-95°C. The crystals were further recrystallized from methanol to give 220 mg of one of the diastereomers as a pure product.

M.p.: 102-105°C

[a]p<5>+32.5° (c=1, chloroform).

IR (KBr) :

2950, 1753, 1634, 1611, 1487, 1354, 1273, 1219, 1180, 1166, 1068, 1042, 990, 919, 899, 862, 840

-1

cm

NMR (CDCl 3 ):

£o.87 (3H, s), 1.12 (3H, s), 1.23 (3H, d, J=6Hz), 1.3-2.7 (711, m) , 3.04 (1H , d, J=15 Hz), 3/24 (3H, s) , 3.35 (3H, s), 3.86 (3H, s) , 3.86 (1H, d, J= 15Hz). 5.15 (1H, q, J=6Hz), 7.04-7.26 (2H, m), 7 , 46-7 , 98 (4H, m) .

For C26H33°7S:

Calculated: C, 63.78; H, 6.79; S, 6.55%

Found: C, 63.66; H, 7.06; S, 6.57%

The second diastereomer was separated from the mixture as a colorless oil by high performance liquid chromatography [column: "Microporasil" manufactured by Waters Co. J column size: 7.8 mm x 30 cm; developing solvent: hexane + ethyl acetate (9:1)].

[α]p5+4.2° (c=0.143, chloroform).

IR (KBr):

2950, 1750, 1631, 1608, 1485, 1352, 1271, 1216, 1172, 1062, 1040, 985, 914, 895, 855, 810 cm"<1>.

NMR (CDCl 3 ):

S 0.91 (3H, s), 1.14 (3H, s), 1.26 (3H, d, J=6Hz), 1.3-2.7 (7H, m), 3.29 (1H , d, J=15Hz), 3.30 (3H,s), 3.42 (3H, s), 3.74 (1H, d, J=15Hz), 3.96 (3H,s), 5, 20 (1H, q, J=6Hz), 7.10-7.30 (2H, m), 7.50-8.02 (4H, m).

EXAMPLE 81

1.922 g (5.000 mmol) of 1-(4-chlorophenyl)-2-(p-toluenesulfonyl-oxy)-1-propanonedimethylacetal and 500 mg (5.00 mmol) of calcium carbonate were heated with stirring at 110°C (bath temperature) for 3 days in a mixture of dimethylformamide and water (4:1 by weight). Usual work-up as in example 36 gave 337 mg of a colorless oil. The oil was found to contain 238 mg of methyl-α-(4-chlorophenyl)propionate by NMR spectroscopy. Dividend 12.0%.

EXAMPLE 82

By a similar procedure as in Example 17, 1-(4-chlorophenyl)-2-hydroxy-1-propanone dimethyl acetal was prepared as a colorless oil from 1-(4-chlorophenyl)-2-bromo-1-propanone. Without further purification, this product was used in the reaction of Example 83.

IR (pure):

3450, 2975, 2930, 1600, 1492, 1398, 1108, 1095, 1052, 1016, 980, 829, 743 cm"<1>.

EXAMPLE 83'

In the same manner as in Example 20, 1-(4-chlorophenyl)-2-(p-toluenesulfonyloxy)-1-propanonedimethyl acetal was prepared as white crystals with a melting point of 76-77°C from 1-(4-chloro-phenyl) -2-hydroxy-1-propanone dimethyl acetal obtained in Example 82, Yield 86% [from 1-(4-chlorophenyl)-2-bromo-1-propanone].

M.p.: 78-79°C (from methanol)

IR (KBr) :

2945, 1601, 1493, 1364, 1347,1195,1188,1094,1057, 1110, 936, 919, 822, 789, 669, 565 cm"<1>.

NMR (CDCl 3 ):

1.05 (3H, d, J=6Hz), 2.40 (3H, s), 3.08 (3H, s), 3.10 (3H, s), 4.93 (1H, q, J= 6Hz), 7.25 (4H, s),

7.27 (2H, d, J=8Hz), 7.76 (2H, d, J=8Hz),

For<C>18H21<S>03C1:

Calculated: C, 56.17;. H, 5.50; Cl, 9.21; S, 8.33% Found: C, 56.22; H, 5.48; Cl, 9.13; S, 8.32%.

EXAMPLE 84

In the same manner as in Example 71, 1-[4-(1-oxo-2-isoindolinyl)phenyl]-2-chloro-1-propanone was prepared as colorless crystals in a yield of 89% from 2-phenyl-1 -isoindolinone and α-chloropropionyl chloride.

EXAMPLE 85

In the same manner as in Example 17, 1-[4-(1-oxo-2-isoindolinyl)phenyl]-2-hydroxy-1-propanone dimethyl acetal was obtained from 1-[4-(1-oxo-2-isoindolinyl) phenyl]-2-chloro-1-propanone in a yield of 83% as colorless crystals with a melting point of 130 - 135°C.

IR (KBr):

3530, 1680, 1515, 1385, 1310, 1120, 1045, 740 cm"<1>.

NMR CDC13):

&0.96 (3H, d, J=7Hz), 2.36 (1H, wide s), 3.20

(3H, s), 3.33 (3H, s), 4.10 (1H, wide q, J=7Hz),

4.80 (2H, s), 7.4-7.6 (5H, m), 7.8-8.0 (3H, m).

For<C>ig<H>21N04:

Calculated: C> 69.70; 11, 6.47; N, 4.28%.

Found: C, 69.63; H, 6.49; N, 4.21%.

EXAMPLE 86

Similarly to Example 73, 1-[4-(1-oxo-2-isoindolinyl)-phenyl]-2-methanesulfonyloxy-1-propanone dimethylacetate was prepared in 95% yield as colorless crystals from 1 -[4-(1-oxo-2-isoindolinyl)phenyl]-2-hydroxy-1-propanone dimethyl acetal and methanesulfonyl chloride.

IR (KBr):

1695, 1520, 1390, 1350, 1340, 1175, 975, 910,

740 cm"<1>.

NMR (CDCl 3 ):

S 1.20 (3H, d, J=7Hz), 3.11 (3H, s), 3.24 (3H, s),

3.30 (3H, s), 4.81 (2H, s), 5.00 (1H, q, J=7Hz), 7.4-7.6 (5H, m), 7.8-8, 0 (3H, m).

EXAMPLE 87

In the same manner as in Example 48, methyl α-[4-(l-oxo-2-isoindolinyl)phenyl]propionate was prepared in a yield of 86% as colorless crystals from 1-[4-(l-oxo-2- isoindolinyl)-phenyl]-2-methanesulfonyloxy-1-propanone dimethyl acetal.

EXAMPLE 88

In the same manner as in Example 17, 1-(4-biphenylyl)-2-hydroxy-1-propanone dimethyl acetal was prepared as colorless crystals with a melting point of 78.5 - 80°C in a yield of 95% from 1-(4- biphenylyl)-2-bromo-1-propanone.

M.p.: 78.5-80°C (from ether/n-hexane)

NMR (CDCl 3 ):

$1.00 (3H, d, J=7Hz), 2.44 (1H, d, J=3.lHz), 3.23 (3H, s), 3.37 (3H, s), 4.12 ( 1H, q,d,J=7Hz , 3.1 Hz), 7.2-7.7 and 7.55 (m and s, 9H)

IR (KBr):

1118, 1102, 1045, 1007, 979, 838, 770, 735, 695

cm 1.

For C17H20<0>3<:>

Calculated: C, 74.97; H, 7.40%

Found: C, 74.88; H, 7.27%

EXAMPLE 89

In the same manner as in Example 7, 1-(4-biphenylyl)-2-methanesulfonyloxy-1-propanonedimethylacetal was prepared as a colorless oil from 1-(4-biphenylyl)-2-hydroxy-1-propanonedimethylacetal . Without purification, this product was used in the reaction in Example 90.

IR (pure):

1490, 1357, 1335, 1177, 1123, 1100, 1065, 1045,' 971, 916, 847, 811, 773, 753, 740, 702, 538, 527 cm 1.

NMR (CDCl 3 ) :

£1.21 (3H, d, J=7Hz), 3.03 (3H, s,), 3.24 (3H, s), 3.31 (3H, s), 5.Ol (1H, q, J=7Hz), 7.1-7.7 (m) -

7.56 (s) total 9H.

EXAMPLE 90

In the same manner as in Example 21, methyl α-(4-biphenylyl)-propionate was prepared as a colorless oil from 1-(4-biphenylyl)-2-methanesulfonyloxy-1-propanone dimethylacetate obtained in Example 89. Yield 80, 5%. [from 1-(4-biphenylyl)-2-hydroxy-1-propanonedimethyl acetal].

NMR (CDCl3):

81.47 (3H, d, J=7Hz), 3.55 (3H, s), 3.68 (1H, q, J=7Hz), 7.1-7.56 (9H, m).

IR (pure):

1741, 1490, 1215, 1167, 765, 701 cm"<1.>

EXAMPLE 91

By a similar procedure to that in Example 57, methyl-α-(4-biphenylyl)propionate was prepared from 1-(4-biphenylyl)-2-methanesulfonyloxy-1-propanonedimethylacetal obtained in Example 89. Yield 68% ([ from 1- (4-biphenylyl)-2-hydroxy-1-propanonedimethyl acetal].

EXAMPLE 9 2

By a similar procedure to that in Example 17, 1,1-dimethoxy-2-hydroxy-1,2,3,4-tetrahydronaphthalene was prepared from 2-bromo-1-oxo-1,2,3,4-tetrahydronaphthalene. Without purification, this product was used in the reaction shown in Example 93.

IR (pure):

1138, 1080, 1058, 767 cm"<1>.

EXAMPLE 9 3

In a similar manner to that described in Example 7, 1,1-dimethoxy-2-methanesulfonyloxy-1,2,3,4-tetrahydronaphthalene was prepared as colorless crystals with a melting point of 113-114.5°C from 1,1-dimethoxy -2-hydroxy-1,2,3,4-tetrahydronaphthalene obtained in Example 92, yield 4 6.5% [from 2-bromo-1-oxo-1,2,3,4-tetrahydronaphthalene).

M.p.: 113-114.5°C (from methylene chloride/diethyl ether/n-hexane)

IR (KBr):

1361, 1340, 1206, 1175, 1141, 1033, 1060, 1050,

981, 959, 949, 917, 847, 781, 768, 625, 546, 530, 510 cm"<1>.

NMR (CDCl 3 ):

S2.37 (2H, m). 2.9 (2H, m) , 2.94 (3H, s) . 2.98

(3H, s), 3.43 (3H, s), 5.27 (1H, t, J=3Hz), 7.17 (3H, m), 7.63 (1H, m) .

For<C>13<H>18<0>5<S:>

Calculated: C, 54.53; H, 6.34; S, 11.20%

Found: C, 54.73; H, 6.36; S, 11.10%

EXAMPLE 94

By a similar procedure as in example 54, methyl indane-1-carboxylate was prepared from 1,1-dimethoxy-2-methane-sulfonyloxy-1,2,3,4-tetrahydronaphthalene. Dividend 4%.

EXAMPLE 9 5

In a similar working method as in example 58, methyl-α-phenylpropionate was prepared in 51.4% yield from 1-phenyl-2-(p-toluenesulfonyloxy)-1-propanone dimethyl acetal and stannous chloride.

EXAMPLE 96

In a similar manner to Example 77, 2-bromo-1-(4-difluoromethoxyphenyl)-1-propanone was prepared as a colorless oil from 1-(4-difluoromethoxyphenyl)-1-propanone.

NMR (CDCl 3 ):

8 1.92 (3H, d, J=7Hz), 5.23 (1H, q, J=7Hz), 6.58 (1H, t, J=72 Hz), 7.15 (2H, d, J =9Hz), 8.00 (2H, d,J=9Hz).

EXAMPLE 9 7

By a similar procedure as in Example 17, 1-(4-difluoromethoxyphenyl)-2-hydroxyl-1-propanone dimethyl acetal was prepared as a colorless oil from 2-bromo-1-(4-difluoromethoxyphenyl)-propanone.

IR (pure):

3600 - 3200, 1515, 1385, 1230, 1130, 1050, 840 cm<-1.>

NMR (CDC13): ...

8 0.95 (3H, d, J=7Hz), 2.37 (1H, d, J=3Hz), 3.23

(3H, s), 3.33 (3H, s), 4.10 (1H, dq, J=3and 7Hz), 6.52 (1H, t, J=74Hz), 7.10 (2H, d, J=9Hz), 7.49 (2 H, d, J=9Hz).

EXAMPLE 98

In a manner similar to that of Example 7, 1-(4-difluoromethoxyphenyl)-2-methanesulfonyloxy-1-propanonedimethylacetai was prepared as a colorless oil from 1-(4-difluoromethoxyphenyl)-2-hydroxy-1-propanonedimethylacetal obtained in Example 97 .Yield 55% [from 1-(4-difluoromethoxyphenyl)-1-propanone].

IR (pure):

1515, 1360, 1235, 1180, 1130, 1100, 1070, 1045, 975, 920, 540, 5 30 cm"<1>.

NMR (CDCl 3 ):

8 1.18 (3H, d, J=7Hz), 3.09 (3H, s), 3.15 (3H,s) 3.18 (3H, s), 4.98 (1H, q, J= 7Hz), 6.53 (1H, t, J= 74 Hz), 7.10 (2H, d, J= 9Hz), 7.45 (2H, d, J=9Hz).

EXAMPLE 99

In a manner similar to that of Example 77, 2-bromo-1-(4-difluoromethoxyphenyl)-3-methyl-1-butanone was prepared as a colorless oil from 1-(4-difluoromethoxyphenyl)-3-methyl-1 -butanone.

IR (pure):

1690, 1605, 1230, 1120, 1055cm"<1>.

NMR (CDCl3):

S 1.02 (3H, d, J=7Hz), 1.21 (3H, d, J=7Hz), 2.1-2.8 (lH, m), 4.85 (1H, d, J=9Hz) , 6.60 (1H, t, J= 74 Hz), 7.18 (2H, d, J=9Hz), 8.03 (2H, d, J=9Hz).

EXAMPLE 100

By a procedure similar to that in Example 17, 1-(4-difluoromethoxyphenyl)-2-hydroxy-3-methyl-1-butanonedimethylacetal was prepared as a colorless oil from 2-bromo-1-(4-difluoromethoxyphenyl) ) -3-methyl-1-butanone.

IR (pure):

3600-3300, 1515, 1390, 1230, 1130, 1050 cm"<1.>

NMR (CDCl 3 )

£0.69 (3H, d, J=6Hz), 0.88 (3H, d, J=6Hz), 1.2-1.7 (1H, m), 2.50 (1H, d, J=3Hz) , 3.22 (3H, s), 3.24 (3H, s), 3.70 (1H, dq, J=3 and 6Hz), 6.50 (1H, t, J=74 Hz), 7, 07 (2H, d, J=9Hz), 7.52 (2H, d, J=9Hz).

EXAMPLE 101

In a manner similar to that of Example 13, 1-(4-difluoromethoxy-phenyl)-2-methanesulfonyloxy-3-methyl-1-butanone dimethyl acetal was prepared as a colorless oil from 1-(4-difluoromethoxy-phenyl)-2-hydroxy- 3-methyl-1-butanone dimethyl acetal.

Yield 76% [from 1-(4-difluoromethoxyphenyl)-3-methyl-1-butanone]. On standing at low temperatures this product crystallized.

Melting point: 60 - 61°C.

IR (KBr):

1515, 1350, 1230, 1180, 1145, 1080, 1055, 1035, 975 cm"<1>.

NMR (CDCl 3 ):

S0.67 (3H, d, J=6Hz), 0.91 (3H, d, J=6Hz), 1.4-1.9 (1H, m), 3.17 (3H, s), 3.19 ( 3H, s), 3.22 (3H, s), 4.75 (1H, d, J=4Hz), 6.50 (1H, t, J=74Hz), 7.08 (2H, d, J=9Hz) , 7.50 (2H, d, J=9Hz).

EXAMPLE 102

By a procedure similar to that in example 54, methyl α-(4-difluoromethoxyphenyl)propionate was prepared in a yield of 51% from 1-(4-difluoromethoxyphenyl)-2-methanesulfonyloxy-1-propanonedimethyl acetal obtained in example 98.

IR (pure):

1745, 1515, 1385, 1230, 1160, 1130, 1050 cm"<1.>

NMR (CDCl 3 ):

S 1.46 (3H, d, J=7Hz), 3.61 (3H, s), 3.67 (1H, q,J=7Hz), 6.43 (1H, t, J=74Hz), 7 .02 (2H,J=9Hz), 7.26 (2H,J=9Hz).

EXAMPLE 103'

0.368 g of 1-(4-difluoromethoxyphenyl)-2-methanesulfonyloxy-3-methyl-1-butanone dimethyl acetal and 0.100 g of calcium carbonate were heated under reflux in 3 ml of a mixed solvent of water and methanol (3:7 by weight) for 18 days. Usual preparation followed by chromatographic separation

gave 0.132 g of methyl α-'(4-difluoromethoxyphenyl)isovalerate as a colorless oil. Yield 51%.

NMR (CDCl 3 ):

6' 0.71 (3H, d, J=7Hz), 1.02 (3H, d, J=7Hz), 2.0-2.5 (1H, m). 3.14 (1H, d, J=llHz), 3.63 (3H, s), 6.47 (1H, t, J=74 Hz), 7.02 (2H, d, J=9Hz), 7 .31 (2H, d, J=9Hz).

EXAMPLE 104

In 3 ml of a mixed solvent of water and DMF (1:4 by weight) 0.368 g of 1-(4-difluoromethoxyphenyl)-2-methanesulfonyloxy-3-methyl-1-butanone and 0.100 g of calcium carbonate were heated at 110° C for 12 days, then refluxed for 3 days. After the usual work-up and separation, 78 mg of methyl α-(4-difluoromethoxyphenyl)isovalerate was obtained. Dividend 30%.

EXAMPLE 105

230 mg of sodium metal was dissolved in 3 ml of anhydrous methanol. An anhydrous methanol solution was added to the solution

(2 ml) of 1.4 3 g of 2-bromo-1-(4-ethoxyphenyl)-3-methyl-1-buta-

nun. The mixture was stirred at room temperature for 1.5 hours then at 50°C for 45 minutes. Usual work-up gave 1.344 g of a crude product of 1-(4-ethoxyphenyl)-2-hydroxy-3-methyl-1-butanonedimethylacetal as a colorless, without further purification, oily substance. The crude product was subjected to the reaction of Example 106.

IR (pure):

3600-3300, 1610, 1515, 1485, 1400, 1250, 1175, 1115, 1050, 990, 925, 840, 810 cm"<1>.

NMR (CDCl 3 ):

5 0.68 (3H, t, J=6Hz), 0.87 (3H, d, J=6Hz), 1.39

(3H, t, J=7Hz), 1.2-1.7 (lH,m), 2.50 (1H, d, J= 3Hz), 3.22 (3H, s), 3.24 (3H , s), 3.68 (1H, dd,

j=3 and 5Hz), 4.01 (2H, q, J=7Hz), 6.82 (2H, d, J= 9Hz), 7.37 (2H, d, J=9Hz).

EXAMPLE 106

In a manner similar to that of Example 13, 1-(4-ethoxyphenyl)-2-methanesulfonyloxy-3-methyl-1-butahonedimethyl acetal was prepared as colorless crystals from 1-(4-ethoxyphenyl)-2-hydroxy-3-methyl-1 -butanone dimethyl acetal obtained in example 105. Yield 62% [from 2-bromo-1-(4-ethoxyphenyl)-3-methyl-1-buta-none].

M.P.: 83 - 87°C.

IR (KBr) :

1610, 1335, 1260, 1245, 1175, 955, 850, 840 cm<*>"<1>.

NMR (CDCl 3 ):

SO.71 (3H, d, J = 6Hz), 0.94 (3H, d, J=6Hz), 1.40 (3H, t, J=7Hz), 1.5-1.9 (lH,m ), 3.18 (3H, s), 3.20 (3H, s), 3.24 (3H, s), 4.02 (2H, q, J=7Hz), 4.57 (1H, d, J=3Hz), 6.85 (2H, d, J=9Hz), 7.37 (2H, d, J=9Hz).

EXAMPLE 107

In 7 ml of a mixture of water and methanol 3:7 by weight)

tele 7.24 mg of 1-(4-ethoxyphenyl)-2-methanesulfonyloxy-3-methyl-1-butanonedimethylacetal and 200 mg of calcium carbonate heated under reflux for 11 hours. After the usual work-up and purification, 467 mg of methyl α-(4-ethoxyphenyl)iso-

valerate obtained as a colorless oil. Yield 99%.

Kp.: 160°C (bath temperature)/17 torr.

NMR (CDCl 3 ):

£0.70 (3H, d, J=6Hz) , 1.01 ( 3H ,d >J = 6Hz) , 1.38 (3H, t, J=7Hz), 2.0-2.6 (lH, m),3.07 (1H, d, J=10Hz), 3.30 (3H, s), 3.97 (2H, q, J=7Hz), 6.80 (2H, d, J=9Hz, 7.20 (2H, d, J=9Hz),

For C14H20<0>3<:>

Calculated: C 71.16; H, 8.53%

Found: C 70.93; H, 8.52%.

EXAMPLE . 108

In a manner similar to that of Example 105, 2.58 g of the crude product of 1-(4-methoxyphenyl)-2-hydroxy-3-methyl-1-butanone-dimethyl acetal was prepared as a colorless oil from 2.71 g of 2 -brorn-1-(4-methoxyphenyl)-3-methyl-1-butanone and subjected to the reaction of Example 109 without purification.

IR (pure):

3600-3300, 1615, 1515, 1255, 1175, 1115, 1045,

840 cm"<1>.

NMR (CDCl 3 ):

8 0.70 (3H, d, J=6Hz), 0.87 (3H, d, J=6Hz), 1.2-1.7 (1H, m), 2.53 (1H, wide s), 3.33 (3H, s), 3.34 (3H, s,), 3.69 (1H, d, J=5Hz), 3.78 (3H, s), 6.83 (2H, d, J =9Hz), 7.40 (2H, d, J=9Hz).

EXAMPLE 109

2.58 g of 1-(4-methoxyphenyl)-2-hydroxy-3-methyl-1-butanone-dimethylacetal obtained in Example 108 was dissolved in 5 ml of anhydrous pyridine and the solution was stirred under ice-cooling. 2.00 g of methanesulfonic anhydride was added to the solution, and the mixtures were stirred for 4 hours under ice cooling, then for 2 hours at room temperature. To the mixture was added 20 ml of water, and the mixture was stirred for 1 hour at room temperature, extracted with 20 ml of diethyl ether three times. The extracts were washed with 5 ml of water twice and dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The oily residue was purified by column

chromatography ("Florisil", methylene chloride) and gave 3.10 g of 1-(4-methoxyphenyl)-2-methanesulfonyloxy-3-methyl-1-butanone-dimethylacetal as a colorless oil (after standing at room temperature. This compound crystallized). Yield 93% [from 2-bromo-1-(4-methoxyphenyl)-3-methyl-1-butanone]. M.p.: 71.5 - 73°G.

IR (KBr) :

1620, 1525, 1355, 1260, 1180, 1105, 1055, 980, 970, 960, 945, 865, 850 cm"1.

NMR (CDCl 3 ):

8 0.69 (3H, d, J=6Hz) , 0.89 (3H, d, J=6Hz)., 1.5-1.9 (1H, m), 3.14 (3H, s), 3.16 (3H, s), 3.21 (3H, s), 3.76 (3H, s), 4.72 (1H, d, J=4Hz), 6.82 (2H,

d, J=9Hz), 7.36 (2H, d, J=9Hz),

EXAMPLE 110

In a manner similar to that of Example 107, methyl α-(4-methoxyphenyl)isovalerate was prepared as a colorless oil from 1-(4-methoxyphenyl)-2-methanesulfonyloxy-3-methyl-1-butanonedimethylacetal. Yield 94%.

IR (pure):

1740,' 1515, 1255, 1160, 1040, 830 cm"<1>.

NMR (CDCl 3 ):

5 0.70 (3H, d, J=6Hz), 1.00 (3H, d, J=6Hz), 2.0-2.6 (lH,m), 3.08 (1H, d, J= 10Hz), 3.63 (3H, s), 3.78 (3H, s), 6.80 (2H, d, J=9Hz), 7.21 (2H, d, J=9Hz).

EXAMPLE 111

To a stirred suspension of 0.65 g of sodium hydride (55% in mineral oil) in anhydrous tetrahydrofuran (10 ml) was added 2.7 ml of ethylene glycol under ice cooling. After stirring for 40 minutes at room temperature, 2.71 g of 2-bromo-1-(4-methoxyphenyl)-3-methyl-1-butanone was added to the reaction mixture and the mixture was stirred for 12 hours at 60°C. After addition of water (50 ml), the reaction mixture was extracted with 30 ml of methylene chloride three times. The extracts were washed with 10 ml of water, dried over magnesium sulfate and concentrated in vacuo. The oily residue was subjected to co-

pocket chromatography ("Florisil", methylene chloride) and gave 719

mg of 2-hydroxy-1-(4-methoxyphenyl)-3-methyl-1-butanoneethylene acetal as a colorless oil. Yield 29%.

IR (pure):

3600-3400, 1620, 1520, 1255, 1175, 1040, 845 cm"<1>.

NMR (CDCl 3 ):

SO,88 (3H, d, J=6Hz) , 0.90 (3H, d, J=6Hz), 1.2-1.7 (1H, m), 2.55 (1H, wide d, J= 5Hz), 3.5-4.2

(5H, m). 3.77 (3H, s), 6.83 (2H, d, J=9Hz), 7.36 (2H, d, J=9Hz).

EXAMPLE- 1, 1<2>

In a manner: similar to that in Example 13, 1-(4-methoxyphenyl)-2-me:fc;ansuMony,loxy-3-methyl-1-butanoneethylene acetal was prepared as a liquid; crystals from 2-hydroxy-1-(4-methoxyphenyl)-3-methyl'-li-bia'tanoneethylene acetal. Yield 78%.

Smp-. : 82 - 83°C.

IR (KBr) :

1610, 1510,, 1335, 1250, 1170, 1050, 970, 940, 930, 815 cm"<1>.

NMR (CDCl 3 ):

8 0.91 (6H, d, J=7Hz), 1.5-1.9 (1H, m), 2.99 (3H,

s), 3.6-4.2 (4H, m), 3.75 (3H, s), 4.67 (1H, d,J= 4Hz), 6.83 (2H, d, J=9Hz) , 7.34 (2H, d, J=9Hz).

EXAMPLE 113

In 5 ml of a mixture of water and methanol (3:7 by weight) 495 mg of 1-(4-methoxyphenyl)-2-methanesulfonyloxy-3-methyl-1-butanoneethylene acetal and 150 mg of calcium carbonate were heated under reflux for 148 hours. After usual work-up followed by column chromatographic purification, 307 mg of 2-hydroxyethyl α-(4-methoxyphenyl)isovalerate was obtained as a colorless oil. Yield 81%.

IR (pure):

3600-3200, 1735, 1610, 1510, 1255, 1170, 1160, 1035, 830cm"<1>.

NMR (CDCl 3 ):

<g>0.70 (3H, d, J=7Hz), 1.03 (3H, d, J=7Hz), 2.0-2.5 (1H, m), 2.27 (1H, wide s ), 3.13 (1H, d, J= 10Hz), 3.5-3>8 (2H, m) , 3.76 (3H, s), 4.0-4.3

(2H, m), 6.81 (2H, d, J=9Hz), 7.21 (2H, d, J=9Hz).

EXAMPLE 114

350 mg of 1-phenyl-2-(p-toluenesulfonyloxy)-1-propanone dimethyl acetal and 0.20 ml of trimethylsilyl trifluoromethanesulfonate were stirred in 1 ml of orthoformate trimethyl ester at 65°C for 9 hours. After normal work-up, methyl-α-phenylpropionate was found to be 50.5% yield by GLC analysis in the same way as in Example 57.

EXAMPLE 115

By a similar procedure as in example 58, methyl-α-phenylpropionate was produced in 80% yield from 1-phenyl-2-(p-toluenesulfonyloxy)-1-propanone dimethyl acetal and iron (II) chloride.

r<g>SAMPLE 116

similarly to Example 80, 1-(6-methoxy-2-naphthyl)-2-(1-10-camphorsulfonyloxy)-1-propanone dlmethyl acetal was prepared as a mixture of two diastereomers from 1-10-camphor -sulfonyl chloride and 1-(6-methoxy-2-naphthyl)-2-hydroxy-1-propanone dimethyl acetal. The mixture was recrystallized twice from methanol to give one of the diastereomers (mp 93-96°C; (oc)<23>D- 32.2 ° (c=0.801, chloroform) as colorless plate-like crystals. This product was in complete agreement with one of the diastereomers of 1-(6-methoxy-2-naphthyl)-2-(d-10-camphorsulfonyloxy)-1-propanonedimethyl acetal obtained in Example 80 ([cx]<25>n+ 32 .5C

(c=l, chloroform)) In IR and NMR spectral data.

The starting material 1-10-camphorsulfonyl was prepared from commercially available ammonium 1-10-camphorsulfonate ([a]<22>-18.4 ° (c=5.3, water)) and thionyl chloride by the method described in [H. Sutherland, and R.L. Shriner, J. Am. Chem. Soc. , 58, 62 (1936)] .

[a]2<6>-32.3 (c=1.36, chloroform)

m.p. 58 - 64 °C

EXAMPLE 117

555 mg of diastereomers of 1-(6-methoxy-2-naphthyl)-2-(1-10-camphorsulfonyloxy)-1-propanonedimethylacetal, which was isolated in Example 116, were reacted in the same manner as in Example 56 to give gl 249 mg of methyl (+ )-α-(6-methoxy-2-naphthyl)propionate. Utilize 90%. [α] 2 ^ +75.0°C (c=0.949, chloroform). IR and NMR spectral data of the product were in agreement

. with those from the product obtained in Example 56.

EXAMPLE 118

799 mg of 1-(6-methoxy-2-naphthyl)-2-hydroxy-1-propanone dimethyl acetal was dissolved in 3 ml of anhydrous pyridine and the solution was stirred at room temperature. To the solution was added 833 mg of p-toluenesulfonyl chloride, and the mixture was stirred at room temperature for 3 days. Water (30 mL) was added and the mixture was extracted with three successive 10 mL portions of methylene chloride. The extracts were dried

over anhydrous magnesium sulfate and concentrated under reduced pressure. The oily residue was purified by column chromatography (silica gel, methylene chloride) to give 1.019 g of 1-(6-methoxy-2-naphthyl)-2-(p-toluenesulfonyloxy)-1-propane dimethyl acetal as a colorless oil.

Yield: 81.9*

IR (pure): 1612, 1489, 1360, 1278,

1192,1178, 899, 560 cm-<1>.

NMR (CDCl 3 ): δ 1.13 (3H, d, J=7 Hz), 2.40 (3H,"s),

3.13 (3H, s), 3.21 (3H, s),

3.88 (3H, s), 5.04 (1H, q, J=7Hz), 7.0 - 7.9 (10H, m).

EXAMPLE 119

To a solution of 132 mg of metallic sodium in 5 ml of anhydrous methanol was added 879 mg of 1-(6-methoxy-2-naphthyl)-2-bromo-1-propanone. The mixture was stirred at room temperature for 7 hours. Water (20 mL) was added and the mixture was extracted with three consecutive 10 mL portions of methylene chloride. Two drops of pyridine were added to the extract and the mixture was dried over anhydrous magnesium sulfate and then concentrated under reduced pressure to give the crude product 1-(6-methoxy-2-naphthyl)-2-hydroxy-1-pr-panonedimethyl-acetal. Without purification, the crude product was dissolved in 2 ml of anhydrous pyridine and the solution was stirred at room temperature. 60 ml of benzenesulfonyl chloride was added to the solution, and the mixture was stirred for 20 hours. Water (10 mL) was added and the mixture was extracted with three consecutive 10 mL portions of methylene chloride. The extracts were washed with 10 ml of water, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The oily residue was purified by column chromatography (silica gel, methylene chloride) to give 1.024 g of 1-(6-methoxy-2-naphthyl)-2-benzenesulfonyloxy-1-propanone dimethyl acetal as a colorless oil. The yield of the product was 82.0%, based on 1-(6-methoxy-2-naphthyl)-2-,rom-1-propanone.

, IR (pure): 1637, 1612, 1488, 1456, 1365,

1278,1190, 925, 900, 761, 598 cm-<1>.

NMR (CDCl 3 ): 1.15 (3H, d, J = Hz);

3.10 (3H, s), 3.18 (3H, s),

5.08 (1H, q, J=7Hz)

7.0 - 8.1 (11H, m).

EXAMPLE 120

Iodotrimethylsilane (0.53 mL, 75 g) was added to 10 mL of methylene chloride under argon and stirred at room temperature.

An anhydrous methylene chloride solution (10 mL) of 1.074 g of 1-(6-methoxy-2-naphthyl)-2-(p-toluenesulfonyloxy)-1-propanone-dimethyl acetal was added to the solution over 20 minutes and the mixture was stirred at the same temperature for 40 minutes. 20 ml of a 20% aqueous solution of sodium thiosulphate was added and the mixture was stirred overnight. The organic layer was washed with five successive 20 ml portions of the same sodium thiosulfate solution as mentioned above, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The remainder was purified by column chromatography! (silica gel, chloroform) to give 495 mg of methyl c-(6-methoxy-2-naphthyl)propionate. Yield 81 <f>. NMR spectral data of the product were in complete agreement with those from the product obtained in Example 54.

Claims (2)

1. Intermediate product for use in the production of an alkanoic acid or ester thereof with formula I: wherein Ar represents phenyl, 4-X-phenyl (where X is chloro, fluoro, isobutyl, tert-butyl, phenyl, acetamino, methoxy, difluoromethoxy, ethoxy or 1-oxo-2-isoindolinyl), 2-thienyl or 6 -methoxy-2-naphthyl; rA represents hydrogen or lower alkyl, or Ar and R<1> together with the carbon atom to which they are attached represent an indanyl group; r<2> represents hydrogen, lower alkyl or lower hydroxyalkyl; characterized by the general formula VI: wherein R 1 represents hydrogen or lower alkyl, R 1 and R 2 independently represent lower alkyl or together the alkylene of 2-6 carbon atoms; Ar^ means a 6-methoxy-2-naphthyl group, a 4-isobutylphenyl group, a 4-lower alkoxyphenyl group, a 4-difluoromethoxyphenyl group, a 2-thienyl group, a 4-(1-oxo-2-isoindolinyl)phenyl group, a 4- biphenylyl group, or a 4-(tert-butyl)phenyl group. 2. Compound according to claim 1, characterized in that it is 1-(6-methoxy-2-naphthyl)-2-hydroxy-1-propanone-dimethyl acetal.