DE1568690C - Process for the production of 17alpha acyloxy 20 keto steroids of the Pregnan series - Google Patents

Description

Various 17oc monoesters of 17 "-hydroxy-20-keto compounds the Pregnan range have a beneficial anti-inflammatory effect, especially Valuable examples of such compounds are described in German Offenlegungsschrift 1,518,915 are. Compounds with anti-inflammatory effects are known to have certain for which Activity necessary substituents in the steroid structure, namely a keto group in the 3-position, 'a Double bond in 4- or 1- and 4-position and either an oxygen function, e.g. B. a Hydroxyin 11ß-position or chlorine both in 9a and 11/9 position. Additional substituents that affect the activity amplify or modify may also be present, e.g. B. a fluorine atom in the 9-position and / or fluorine atoms, methyl and hydroxyl groups, e.g. B. in 2,6- or 16-position.

It is an object of the present invention to provide a convenient method for making such 17oc monoesters to create compounds that have an additional hydroxide group in the skeleton, as in 11 position. Such attempts to acylate a ll / ^ na-dihydroxy-10-keto-pregnane compound in a position generally do not lead to a satisfactory result, and often an additional as occurs Acylation in 11-position.

17 "monoesters of 17a, 21-dihydroxy-20-keto steroids can be prepared in a comparatively simple manner by using the 17 <x, 21-dihydroxy compound first converted into a 17a, 21-orthoester, which is then converted with acid to the 17a-monoester can be hydrolyzed (see US Pat. No. 3,152,154). This manufacturing process brings in general there is only a small risk that a hydroxyl group which may be present in the 11-position is acylated.

The present invention relates to a process for the preparation of a 17a-acyloxy steroid of the pregnane series with the partial structure in position 17:

CH ₃

40

CO

OCOR

(H)

45

that consists in getting a 21-yo "d-17a acyloxysteroid the Pregnan series with the partial structure in position 17:

CHoJ

CO

(III)

OCOR

55

where R in the partial structures (II) and (III) is an alkyl, cycloalkyl, cycloalkylalkyl or aralkyl radical means with a tertiary amine or dialkyl sulfoxide heated, or that a pregnane compound with the partial structure in the 17-position:

CHoX

CO

(D

65

OCOR

in which X is a hydrocarbon sulfonyloxy radical or a bromine atom and R is an alkyl, cycloalkyl, Cycloalkylalkyl or aralkyl radical means with a metal iodide such as an alkali or alkaline earth metal iodide Heated in the presence of a tertiary amine or a dialkyl sulfoxide.

The radical R preferably represents a low molecular weight alkyl group having 1 to 7 or more carbon atoms represent.

The cycloalkyl radicals preferably contain 5 or 6 carbon atoms, and the cycloalkylalkyl radicals represent preferably a cycloalkylmethyl group.

As examples of tertiary amines that can be used, pyridine, Collidine, dimethylanylin and tri-lower alkylamines such as triethylamine or tripropylamine. As examples for dialkyl sulfoxides, the lower alkyl sulfoxides such as dimethyl sulfoxide can be mentioned.

If necessary, the above reactions can be carried out in the presence of an additional inert solvent and preferred inert solvents include ketones such as acetone and methyl ethyl ketone, alkanols such as ethanol, methanol and isopropanol, and substituted amide solvents, like dimethylformamide.

The hydrocarbon residue of the sulfonyl group can be a convenient alkyl, aryl, or alkaryl group such as be a low molecular weight alkyl or lower alkylaryl radical, in particular one whose alkyl moiety Contains 1 to 6 carbon atoms, such as methyl or p-tolyl etc.

The conversion of compound I into compound II or compound III in compound II is preferably effected by heating at temperatures of 60 to 120 ⁰ C, if necessary under pressure, the boiling point of the tertiary amine, SuIfoxyds or solvent low is when the reaction temperature employed. A convenient reaction temperature is 100 ° C, or optionally the boiling point of the tertiary amine, dialkyl sulfoxide or solvent, if this is below 100 ° C.

21-bromine compounds of the general formula I can be prepared by the corresponding 21-hydrocarbyl sulfonyloxy compounds with an alkali or alkaline earth bromide such as sodium, lithium or calcium bromide under anhydrous Reacts conditions in a solvent such as acetone, ethanol, acetonitrile or dimethylformamide. This reaction is preferably carried out at temperatures from 50 to. 120 ° C and conveniently at the boiling point of the solvent used causes. In general, relatively long reaction times are required, which can extend to several days.

The 21-iodine compounds of the formula III can be prepared either directly from the corresponding 21-hydrocarbyl sulfonyloxy compounds or from the corresponding 21-bromine compounds, the latter method being preferred over the previously mentioned method. The direct formation of the 21-iodine compound either from the hydrocarbyl sulfonyloxy compound or from the 21-bromine compound is effected by heating with an alkali metal or alkaline earth metal iodide in the presence of a solvent such as acetone, ethanol, acetonitrile or dimethylformamide. The reaction is preferably carried out at temperatures from 50 to 120 ^° C. and conveniently at the boiling point of the solvent used. The conversion de:

Gen in the 21-Jodverbindun _r 21-sulfonyloxy is slow and often incomplete even after 8 days. On the other hand, formation from the bromide takes place relatively quickly, reaction times of, for example, 12 hours often being sufficient, depending on the reaction temperature used.

The 21-hydrocarbyl sulfonyloxy compounds can be prepared from the corresponding 21-hydroxy compounds in a conventional manner, e.g. B. by reaction with a hydrocarbon sulfonyl halide in the presence of a tertiary base like pyridine.

The methods of the invention are particularly valuable for the manufacture of various 17 <x monoesters of 21-deoxybetamethasone and 21-deoxydexamethasone, e.g. B. of compounds of following general formula:

CH ₃

in which R ^{2 is} a straight or branched chain alkyl radical with 1 to 9 carbon atoms and in particular an alkyl radical which contains a straight chain with up to 3 carbon atoms, which can be branched with a methyl group, and in particular of compounds that are listed in German publication 1 518 915 are described.

The methods of the invention are also useful in the preparation of A ⁹ pregnan compounds. These compounds can be prepared by adding a 17 ", 21-diol via e ^; NEN 17 ^, 21-orthoester converts into the corresponding 21-oI-17a-acyloxy compound, converts this into a 21-hydrocarbyl sulfonyloxy compound of the formula (I) and then further processed according to the process according to the invention. The zl ⁹ -Ausgangssubstanzen are also useful for the conversion into the compounds of formula (IV) in which R ^a is as defined hereinbefore.

For example

a) 9Ä-FluoΓ-ll /? - hydroxy.-21-methanesulfonyloxylo / J-methyl-nix-propionyloxypregna-l ^ -dien-

3,20-dione

5.3 g of 9 "-fluoro-II / 3,21-dihydroxy-16y3-methyl-17" -propionyloxypregna-1,4-diene-3,20-dione in 20 ml of pyridine were treated with 5 ml of methanesulfonyl chloride, and that The mixture was allowed to stand at room temperature for 15 minutes. Then it was poured into ice-cold η-hydrochloric acid with stirring. The 21-methanesulfonate was filtered off and crystallized from aqueous ethanol to give 4.5 g of the product; F. = 177 to 179 ⁰ C, [x] _D = + 80 ° (c = 0.5, CHCl ₃ ), Xmax (in ethanol = 238 to 240 παμ (ε = 14 800).

Analysis: C ₂₆ H ₃₅ FO ₈ S · ¹ I ₂ H ₂ O.

Calculated .... C 58.2%, H 6.8%;
found .... C 58.2%, H 7.0%.

b) gß 17 "-propionyloxypregna-1,4-diene-3,20-dione

1 g of 9 * -Fluor-II / 9-hydroxy-21-methanesulfonyloxy-16jS-methyl-17 «rpropionyloxypregna-1,4-diene-3,20-di- on in 50 ml of pyridine was treated with 3 g of sodium iodide, and the mixture was left for 6 hours. at 100 ° C heated. It was then poured into dilute hydrochloric acid and extracted with chloroform. the

ίο extract was washed sequentially with aqueous sodium bicarbonate, aqueous sodium thiosulfate and water, dried (MgSO ₄ ) and evaporated to dryness. The residue was chromatographed on 50 g of neutral aluminum oxide (grade III); that

Material eluted with ether-benzene (1: 3) was crystallized from acetone-hexane to give 270 mg of 9 <x -fluoro-11/3-hydroxy-16/5-methyl-17a-propionyloxypregna-1,4-diene-3 , 20-dione; F. = 238 to 241 ° C, [«] _β = + 75 ° (c = 1.0 in CHCl ₃ ).

Example 2

a) 9 "-Fluoro-11j8-hydroxy-21-methanesulfonyloxy-16/5-methyl-17a-valeryloxypregna-1,4-diene-3,20-dione

A solution of 2 g of 9 <x-fluoro-II / 9,21-dihydroxy-16 /? -Methyl-17 "-valeryloxypregna-1,4-diene-3,20-dione in 17.2 ml of pyridine was produced Cooled 0 ° C and treated with 1.72 ml methanesulfonyl chloride. After standing at 0 ° C. for 15 minutes, the mixture was poured into ice-cold 0.5 η hydrochloric acid and the precipitate was collected and washed with sodium bicarbonate and water. The product was dried in vacuo over potassium hydroxide at room temperature to give 2.25 g of methanesulfonate as an amorphous solid; F. == about 76 ° C (decomposition), [a] _ö = + 71.0 ° (c = 1.3 in dioxane), X _max (in ethanol) = 239 ηιμ (ε = 15 580).

Analysis: C ₂₈ H ₃₉ FO ₈ S.

Calculated .... C 60.6%, H 7.1%, S 5.8%; found .... C 60.45%, H 7.4%, S 5.8%.

b) 21-Bromo-9 * -fluoro-ll £ -hydroxy-16/9-methyl-17 "-valeryloxypregna-1,4-diene-3,20-dione

A solution of 4 g of 9 * -fluoro-llje-hydroxy-21-methanesulfonyloxy -16/9 - methyl -17 * - valeryloxypregnal, 4-diene-3,20-dione. in 200 ml of acetone was treated with 12 g of anhydrous lithium bromide and the mixture was refluxed for 3 days. The acetone was removed in vacuo and the residue partitioned between chloroform and water. After evaporation and crystallization from ether, the chloroform fraction gave 3 g of the 21-bromine compound in the form of prisms; F. = 148 to 149 ° C (decomposition), [x] d = + 99.3 ° (c = 1.6 in dioxane), ?. _max (in ethanol) = 238 to 239 ιημ (ε = 16,620).

Analysis: C ₂₇ H ₃₆ BrFO ₅ .

Calculated .... C 60.1%, H 6.7%, Br 14.8%; found .... C 60.5%, H 6.9%, Br 14.6%.

c) 9 * -Fluoro-II / S-hydroxy-21-iodine-16/9-methyl-173i-valeryloxypregna-1,4-diene-3,20-dione

(1) A solution of 1.66 g of 21-bromo-9ic-fluoro-1 l /? - hydroxy-l 6/9-methyl-17 x-valeryloxypregna-1,4-diene-3,20-dione in 75 ml of acetone was treated with 3.3 g of sodium iodide and the mixture under overnight Heated to reflux. The acetone was de-

removed and the residue distributed between ether and water. After evaporation and crystallization of the residue from aqueous acetone, the ether fraction gave 1.53 g of the 21-iodine compound in the form of fine needles; F. - 129 to 13O ⁰ C (decomposition), [<\] "= I 106.2 ° (c = 1.4 · in dioxane), l _max (in ethanol) = ■. 237 to 239 πιμ (e = 16 480).

Analysis: C ₂₇ H ₃₆ FJO ₅ .

Calculated .... C 55.3 ° / ₀ , H 6.2%, J. 21.6%; found .... C 55.8%, H 6.45%, J 21.1%.

(2) A solution of 200 mg of 9 * -fluoro-II / 3-hydroxy-21 - mclhansulfonyloxy -16/3 - methyl - 17α - valeryloxypregna-1,4-diene-3,20-dione in'5 ml of acetone was treated with 400 mg of sodium iodide and the mixture refluxed on a steam bath. After 8 days it had about 75% conversion to 21-iodine compound occurred as from the intensity the spot was closed by thin layer chromatography.

d) 9A-fluoro-II /? - hydroxy-16 /? - methyl-17 \ -valeryloxypregna-1,4-diene-3,20-dione

(1) A solution of 50 mg of 9a-fluoro-II / 3-hydroxy-21-j od -16/3-methyl -1 7λ-valeryloxypregna-1,4-diene-3.20-dione in 1.25 ml of pyridine was made heated on the steam bath for 3 and ₂ hours. The mixture was poured into water and extracted with chloroform, and the isolated material (40 mg) was chromatographed on neutral aluminum oxide (grade IV) and gave, after elution with ether and crystallization from benzene-petroleum, 15 mg of 9-fluoro-11/3 -hydroxy-16/9-methyl-17. \ - valeryloxypregna-1,4-diene-3,20-dione.

(2) A solution of 300 mg of 9 \ -fluoro-II / 3-hydroxy-21-iodo-16/3-methyl-17λ -valeryloxypregna-1,4-diene-3,20-dione in 13 ml of dioxane was mixed with 10 ml of a 5% aqueous sodium metabisulfite solution and the mixture was heated on the steam bath for 1 hour. The mixture was diluted with water and evaporated to a small volume. The white crystalline precipitate was isolated and dried and gave 220 mg of 9. \ - fluoro-11 ^ -hydroxy-16 / i-methyl-17. \ - valeryloxypregna-1,4-diene-3,20-dione; M.p. = 195 ° C, [a] d = + 69.2 ° (c = 1.4 in CHCl ₃ ).

B e i s ρ i e 1 3

9 \ -FUior-II / 3-hydroxy-16/9-methyl-17a-valeryloxypregna-1,4-diene-3,20-dione

A solution of 500 mg 9. \ - Fluoro-II / 3-hydroxy-21-methanesulfonyloxy -16 / 3-methyl-17λ-valeryloxypregna-1,43,20-dione in 12.5 ml of pyridine was mixed with 1 g Sodium iodide and the mixture heated on the steam bath for 6 hours. The mixture was poured into water and the solid (383 mg) isolated by filtration. Chloroform extraction of the filtral gave a further fraction (30 mg) of the product. The combined solids were taken up in acetone and nitrated over llorisil (magnesium trisilicate) to remove some of the color, and the residue was chromatographed in benzene on 5.5 g of neutral aluminum oxide (grade IV). Elution with ether and double crystallization of the fractions from benzene-petroleum gave 171 mg of 9-fluorine-II / S-hydroxy-U) /) '-methyl-17-valeryloxypregna-1,4-diene-3,20-dionine I-oim of fine needles; F. = 195 to 196 ^C C, Ho = 64.9 "(<· 1.3 in CHC1 _{; 1} ). The infrared spectrum of the product was identical to that of an authentic sample.

Example 4

9a-fluoro-l 1/3-hydroxy-l 6/3-methyl-l 7a-valeryloxypregna-l, 4-diene-3,20-dione from 9 "-Fluor-II / S-hydroxy-Zl-iodo-lojff-methyl-na-valeryloxypregna-l ^ -diene-3,20-dione

(a) With pyridine

A solution of 50 mg of 9a-fluoro-II / 3-hydroxy-21-iodine -16/9-methyl-17α-valeryloxypregna -1,4-diene-3,20-dione in 2 ml of pyridine was on the steam bath for 3 hours heated. The mixture was evaporated to dryness, dissolved in chloroform and applied to a small column of neutral alumina (grade IV). The column was eluted with ether, and the product obtained was crystallized from chloroform-petroleum to give 27 mg, corresponding to a yield of 69 ⁰ ^ _0, 9a-fluoro-ll / 3-hydroxy-16j9-methyl-17ix-valeryloxypregna-l , 4-diene-3,20dione with an infrared spectrum identical to that of an authentic sample.

(b) With triethylamine

A solution of 50 mg of the 21-iodine compound in 2 ml of triethylamine was left on the steam bath for 5 hours heated and then worked up as in Example 4 (a). Crystallization from chloroform-petroleum resulted 32.7 mg, corresponding to a yield of 83.5%, 9λ-fluoro-II / 3-hydroxy-16 /? -Methyl-17a-valeryloxypregna-1,4-diene-3,20-dione with an infrared spectrum identical to that of an authentic sample.

(c) With dimethyl sulfoxide

A solution of 50 mg of the 21-iodine compound in 2 ml of dimethyl sulfoxide was heated on the steam bath for 20 hours and in the usual way ^; se worked up, whereby an oily solid was obtained. This product was purified by preparative thin layer chromatography and gave about 5 mg of unchanged 21-iodine compound and 24.5 mg, corresponding to a 62.5% yield, 9a-fluoro-II / S-hydroxy-16/3-methyl-17a-valeryloxypregna-I , 4-diene-3,20-dione.

Example 5

9a-fluoro-II / 3-hydroxy-16/3-methyl-17a-valeryloxypregna-1,4-diene-3,20-dione from 21 -Bromo-9α-fluoro-II / S-hydroxy-loß-methyl-na-valeryloxypregna-l ^ -diene-3,20-dione

(a) With sodium iodide in pyridine

A solution of 50 mg of 21-bromo-9a-fluoro-II / 3-hydroxy-16/3 - methyl - 17α - valeryloxypregna -1,4 - diene 3,20-dione and 100 mg sodium iodide in 2 ml Pyridii was heated on the steam bath for 3 hours. The pyridine was removed in vacuo and the residue ir Chloroform filtered through a small layer of neutral: grade IV aluminum oxide. The sliding was washed with ether, the washing water combined and evaporated, whereby 30 mg,. Corresponding 70% yield, 9th \ - fluoro-II / 3-hydroxy-16/3-methyl 17A-valeryloxypregna-1,4-diene-3,20-dione with an infrared spectrum that matches that of an authentic sample was identical, were obtained.

(b) With sodium iodide in triethylamine

A suspension of 50 mg of 21-bromo-9. \ - fluo! 1 l /? - hydroxy-16 / i-melhyl-17 "-valeryloxypregna-1,4-d cn-3,20-dione and 100 mg of sodium iodide in 2η triethylamine was on the steam bath for 8 hours

heated. The solvent was removed in vacuo and the residue treated as above, whereby 39.6 mg, corresponding to 93 ° / ₀ yield, 9a-fluoro-ll / S-hydroxy-16jö-methyl-17a-valeryloxypregna-l, 4-diene- 3,20-dione were obtained.

7 g of methanesulfonate in 200 ml of pyridine was treated with 14 g of sodium iodide and the mixture became heated on the steam bath for 5 hours. The pyridine was removed in vacuo and the dark, oily one Dissolved residue in chloroform and filtered through silica gel. The silica gel was washed with ether which Wash waters were evaporated to give a yellowish crystalline solid. Crystallization this Material from ether and then from ether — Pe-

(c) With sodium iodide in triethylamine-acetone

A solution of 50 mg of 21-bromo-9 «-fluoro-II / 9-hydroxy-16/9 - methyl - 17α - valeryloxypregna -1,4 - diene-3,20-dione and 100 mg of sodium iodide in 1.5 ml Acetone io troleum gave 2.88 g of loß-methyl-na-propionyloxy- and 1.5 ml of triethylamine was pregna-1,4,9-triene-3,20-dione as silky needles on the steam bath; Heated for 18 hours. The work-up happened like
described above and yielded 39.6 mg, accordingly
93% yield, 9a-fluoro-II /? - hydroxy-16/9-methyl-

15th

17 «-valeryloxypregna-1,4-diene-3,20-dione. Example6

• (a) 16 / S-methyl-i7 «, 21 (l'-ethyl-l'-ethoxymethylene

dioxy) -pregna-1,4,9-triene-3,20-dione A solution of 500 mg 17a, 21-dihydroxy- so 16/3-methylpregna-1,4,9-triene-3,20-dione in 20 ml of dioxane was treated with 0.7 ml of triethyl orthopropionate and about 5 mg of p-toluenesulfonic acid. After

F. = 177 to 179 ° C, [<x] _D = + 2.7 ° (c = 1.1 dioxane), (in ethanol) = 237 to 238 πιμ (ε = ■ 15 580).

Analysis: C ₂₅ H ₃₂ O ₄ .

Calculated .... C 75.7%, H 8.15%; found .... C 75.75%, H 8.1%.

B e i s ρ i e 1 7

(a) 9 "-Fluoro-II / 3,21-dihydroxy-16" -methyl-17-propionyloxypregna-I , 4-diene-3,20-dione

(Dexamethasone 17-propionate) 5 g of dexamethasone was dissolved in 200 ml of dioxane and with 400 mg p-toluenesulfonic acid and 20 ml tri-

Let stand at room temperature for 40 minutes

the mixture was added to dilute sodium bicarbonate 25 äthylorthopropionat. The solution was solution poured and the product left to stand by filtration for 1 hour at room temperature and

isolated. Crystallization from ether gave 340 mg of 16 / S-methyl-17a, 21- (l'-ethyl-l'-ethoxymethylenedioxy) -pregna-1,4,9-triene-3,20-dione in the form of cubic prisms, F. . = 175 to 177 ° C, [<x] _D = + 5.2 ° (c = 1.0,

Dioxane), X _max (in ethanol) = 238 to 239 ΐημ (ε = 16,000).
Analysis: C ₂₇ H ₃₈ O ₅ .

Calculated
found

(b)

C 73.6%, H 8.25%; C 73.4%, H 8.5%.

then poured into sodium bicarbonate solution. The white precipitate was filtered off and dried at 100 ⁰ C to give 5.83 g of dexamethasone 17,21-äthylorthopropionat.

This product was dissolved in 240 ml of acetone, and 48 ml of water and 2.4 ml of 2η-sulfuric acid were added. The solution was left to stand at room temperature for 30 minutes and then poured into water; the product was isolated with chloroform. The crude product was crystallized from acetone-hexane and gave 3.6 g of 9'-fluorine-II / J, 21-dihydroxy-16a-methyl-17-propionyloxypregna-1,4-diene-3,20-dione; M.p. = 219 to 223 ° C, [oc] _D = -6 ° (c = 1.0 in CHCl ₃ );

21-Hydroxy-16 ^ -methyl-17 "-propionyloxypregna-1,4,9-triene-3,20-dione

Uncrystallized 16 £ -Methyl-17 ", 21- (l'-ethyl- 40 λ _Μαχ = 238 ΐημ (EB! .. =. 351). L'-ethoxymethylenedioxy) -pregna-1,4,9-triene-3 , 20-dione, Analvse · CH FO that from 8.0 g of 17 «, 21-dihydroxy-16, S-methylpregna- J ·« m. «·

1,4,9-triene-3,20-dione, as described in Example 6 (a), was dissolved in 95 ml of acetic acid containing 8 ml of water and allowed to stand at room temperature for 40 minutes. Dilution with water and filtration gave the crude product. Crystallization of this product from ether (which contained some acetone) - petroleum gave 7.52 g of 21-hydroxy-16 /? - methyl-calculated
found

C 67.0%, H 7.4%; C 67.25%, H 7.0%.

(b) 9α-fluoro-ll _ί S-hydroxy-21-methanesulfonyloxy-16 "-methyl-17-propionyloxypregna-l, 4-diene-3,20-dione

3 g of dexamethasone-17-propionate pyridine were dissolved in 30 m, and the solution was heated to - 10 ⁰ C

17oc-propionyloxypregna-1,4,9-triene-3,20-dione in Form 50. 3 ml methanesulfonyl chloride were added to von large prisms, m.p. = 177 to 179 ° C [<x] _D = + 16.1 ° and the temperature at about 20 ° C for 30 minutes

held. The reaction mixture was poured into cold, dilute 2η hydrochloric acid and the white

(c = 0.9 dioxane), l _max (in ethanol) = 237 to 238 ηιμ. (ε = 16 210).

Analysis: C ₂₅ H ₃₂ O ₅ .
Calculated .... C 72.8%, H 7.8%; found .... C 73.0%, H 7.9%.

(c) 16/3-methyl-17 (x-propionyloxypregnal, 4,9-triene-3,20-dione

A solution of 6.7 g of 21-hydroxy-16/3-methyl-17a-propionyloxypregna-1,4,9-triene-3,20-dione in 50 ml of dry pyridine was at 0 ° with 1.87 ml of methanesulfonyl chloride treated. After standing at room temperature for 1 hour, the mixture became under Stir poured into ice-cold η-hydrochloric acid. Filtration gave 7.9 g, corresponding to a 99% yield, 21-methanesulfonate as a white amorphous solid.

Precipitation
was then

filtered off and dried (3.3 g). It crystallizes from acetone-hexane and has a ^{temperature of 183 to 186 0} C (c = 1.0 in CHCl ₃ );

gave 2.9 g methanesulfonate;
(Decomposition); [<x] _D = + 46 °
Imax = 238 ΐημ (ElS _n = 308).

Analysis: C ₂₈ H ₃₅ FO ₈ S.
Calculated .... C 59.3%,
found C 59.6%,

H 6.7%, S 6.1%; H 6.5%, S 6.1%.

(c) 9 "-fluoro-llje-hydroxy-16" -methyl-

17-propionyloxypregna-1,4-diene-3,20-dione (21-deoxydexamethasone-17-propionate)

500 mg of 9a-fluoro-II (3-hydroxy-21-methanesulfonyloxy - 16ä - methyl -17 - propionyloxypregna -1,4- diene-

209 610/91

3,20-dione was dissolved in 25 ml of paridine, and 2.5 g of sodium iodide were added. The solution was heated in an oil bath which was kept at 105 ^° C. for 17 hours and was then cooled and poured into cold 2η hydrochloric acid and extracted with chloroform. The extract was washed with water, sodium thiosulfate solution and water and dried _{over MgSO 4.} The solution was then evaporated and the residue crystallized from acetone-hexane to give 140 mg of 21-deoxydexamethasone-17-propionate; M.p. = 216 to 219 ° C; [a.] _D z = + 50 ° (c = 1 in CHCl ₃ ), X _max = 239 ηαμ (eff. = 367).
Analysis: C ₂₅ H ₃₃ FO ₅ .

Calculated .... C 69.3%, H 7.7 "/"; found ..... C69,4 ° / _0, H7,5 ° / _o.

Claims (1)

Claim: Process for the preparation of 17 "-acyloxy-20-keto-steroids the Pregnan row of the partial structure in position 17 CH ₃ characterized in that (A) a 21-iodine-17 "-acyloxysteroid of the pregnane series of the partial structure in the 17-position CH ₂ J CO OCOR (III) where R in formulas (II) and (III) is an alkyl, cycloalkyl, cycloalkylalkyl or aralkyl radical means heated with a tertiary amine or a dialkyl sulfoxide, or (B) that one a pregnane compound of the partial structure in the 17-position CH "X CO OCOR CO OCOR (Π) in which X is a hydrocarbon sulfonyloxy radical or a bromate and R is an alkyl, cycloalkyl, Cycloalkylalkyl or aralkyl radical means with a metal iodide in the presence of a tertiary one Amine or a dialkyl sulfoxide heated.