DE1568690B - Process for the production of 17alpha acyloxy 20 keto steroids of the Pregnan series - Google Patents

Description

1 2

Various 17 «monoesters of 17a-hydroxy in which X is a hydrocarbon sulfonyloxy radical

20-keto compounds of the pregnane series have one or one bromine atom and R an alkyl, cycloalkyl,

useful anti-inflammatory effect, being cycloalkylkyl or aralkyl radical, with a

especially valuable examples of such compounds in metal iodide such as an alkali or alkaline earth iodide in

German Offenlegungsschrift 1 518 915 describes the presence of a tertiary amine or a dialkylbene are. Compounds heated with anti-inflammatory sulfoxyds.

It is known that certain effects have effects for which the radical R preferably represents a low molecular weight

Activity necessary substituents in the steroid skeleton. Alkyl group with 1 to 7 or more carbon atoms

on, namely a keto group in the 3-position, a.

Double bond in 4- or 1- and 4-position and ent- io The cycloalkyl radicals preferably contain 5 or neither an oxygen function, eg. B. a hydroxy 6 carbon atoms, and the cycloalkylalkyl radicals are in the 11/3 position or chlorine in both the 9 <x and len is preferably a cycloalkylmethyl group.
11/3 position. Additional substituents which may also be mentioned, pyridine, may be present, e.g. B. a fluorine atom in the 9-position and / 15 Coüidin, dimethylanylin and tri-lower alkylamines or fluorine atoms, methyl and hydroxyl groups, such as triethylamine or tripropylamine. As examples z. B. in 2.6 or 16 _T position. the lower alkyl sulfoxides can be used for dialkyl sulfoxides

It is an object of the present invention to be named as dimethyl sulfoxide,

quemes process for the production of such Πα-Μοηο- The above reactions may be required-

to create esters of compounds that have an additional 20, if in the presence of an additional inert solution

Liche hydroxide group in the skeleton, as carried out in means, and to be preferred 11 position. Such attempts at acylating an inert solvent include ketones such as acetone

ll / ?, 17a-dihydroxy-20-keto-pregnane compound inl7 <% - and methyl ethyl ketone, alkanols such as ethanol, meth-

Position generally do not lead to a zuanol and isopropanol, and substituted amide solution

satisfactory result, and often an additional agent such as dimethylformamide occurs.

Acylation in 11-position. The hydrocarbon residue of the sulfonyl group can

17 «-monoester of 17a, 21-dihydroxy-20-ketostero- a convenient alkyl, aryl or alkaryl group, such as

iden can be used in a comparatively simple manner as a low molecular weight alkyl or lower alkylaryl

can be produced by the 17a, 21-di- residue, in particular one whose alkyl moiety

hydroxy compound initially in a 17 ", 21-ortho 30 contains 1 to 6 carbon atoms, such as methyl or

ester, which is then converted with acid to the 17 «-mono-p-tolyl, etc.

ester can be hydrolyzed (see. USA.-Patent- The conversion of compound I in. Verbinschrift 3 152 154). This manufacturing method involves dung II or compound III in compound II is generally only a slight risk, that is preferably by heating at temperatures of an existing optionally in the 11-position hybrid 35 causes from 60 to 120 ⁰ C, if necessary acylated droxygruppe will. Pressure, where the boiling point of the tertiary amine, The present invention relates to a process for sulfoxide or solvent is lower than the preparation of a 17a-acyloxysteroids the pregnancy applied reaction temperature. A convenient series with the partial structure in the 17-position: action temperature is 100 ° C or optionally the ££ j 40 boiling point of the tertiary amine, dialkyl sulfoxide or ι ³ solvent, if this is below 100 ° C. '21-bromine compounds of the general formula II (II) can be prepared by the fact that

1 "OCOR-speaking 21-hydrocarbon sulfonyloxy compound

17 45 fertilize with an alkali or alkaline earth bromide such as

Sodium, lithium or calcium bromide under water

that consists in that one 21-iodine-17a-acyloxy-free conditions in a solvent such as acetone,

converts steroid of the pregnane series with the partial structure in ethanol, acetonitrile or dimethylformamide.

17-position: This reaction is preferably carried out at temperatures

CH ₂ J 50 from 50 to 120 ⁰ C and conveniently at the boiling point

I of the solvent used causes. In general

/ _TTT \ n ^{en sm} d relatively long response times required,

^ ' which can extend to several days.

/ \ The 21-iodine compounds of the formula III can

17 55 either directly from the corresponding 21-carbon

hydrogen sulfonyloxy compounds or from the

where R in the partial structures (II) and (III) a corresponding 21-bromine compounds are produced

Alkyl, cycloalkyl, Cycloalkyialkyl- or aralkyl radical, the latter method compared to the

means, with a tertiary amine or dialkyl sulf previously mentioned the preference is given,

oxide heated, or that a pregnane compound 60 The direct formation of the 21-iodine compound either

with the partial structure in the 17-position: from the hydrocarbyl sulfonyloxy compound or

from the 21-bromine compound becomes by heating with

CH ₂ X an alkali or alkaline earth iodide in the presence of one

I solvents such as acetone, ethanol, acetonitrile or

/ τ-. ⁶ 5 dimethylformamide causes. The implementation will

^ ' preferably at temperatures from 50 to 12O ⁰ C _and conveniently at the boiling point of the use

17 ^N solvent carried out. The transformation of the

21-sulfonyloxy compounds into the 21-iodine compounds occurs slowly and is often incomplete even after 8 days. Formation from the bromide takes place relatively quickly, however, reaction times of, for example, 12 hours are often sufficient, which of the reaction temperature used depends.

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 "monoesters of 21-deoxybetamethasone and 21-deoxydexamethasone, e.g. B. of compounds of following general formula:

CH ₃

in which R ^a 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 described in German Offenlegungsschrift 1 518 915 are described.

The processes of the invention are also useful in the preparation of Δ "-pregnan compounds. These compounds can be prepared by converting a 17", 21-diol via e-'nen 17a, 21-orthoester into the corresponding 21-ol-17 " 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 A ^B starting substances are also useful for the conversion into the compounds of the formula (IV), in which R ^a the above has given meaning.

example 1

a) 9 "-Fluor-1 l /? - hydroxy-21-methanesulfonyloxy-

Lö / J-methyl-lTa-propionyloxypregna-l ^ -dien-

3,20-dione

5.3 g of 9a-fluoro-II / ?, 21-dihydroxy-16 ^ -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, [oc] _D = + 80 ° (c = 0.5, CHCl ₃ ), Imax (in ethanol = 238 to 240 πιμ (ε = 14 800).

Analysis: C ₂₈ H ₃₅ FO ₈ S • Va H ₂ O.

Calculated .... C 58.2%, H 6.8%;
found .... C58,2 _^9/0, H 7.0%.

b) 9a-fluoro-11E-hydroxy-16/9-methyl-17 "-propionyloxypregna-1,4-diene-3,20-dione

1 g of 9α-fluoro-II / ^ hydroxy-21-methanesulfonyloxy-16/3-methyl-17 "-propionyloxypregna-1,4-diene-3,20-di- on in 50 ml of pyridine was treated with 3 g of sodium iodide, and the mixture was stirred for 6 hours 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 9α-fluoro-II / 9-hydroxy-16 / S-methyl-17α-propionyloxypregna-1,4-diene-3.20 -dione; F. = 238 to 241 ⁰ C, [a] _D = + 75 ° (c = 1.0 in CHCl ₃ ).

Example 2

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

A solution of 2 g of 9a-fluoro-II / ?, 21-dihydroxy-16 /? -Methyl-17 "-valeryloxypregna-1,4-diene-3,20-dione in 17.2 ml of pyridine was heated to 0 ° C cooled and treated with 1.72 ml methanesulfonyl chloride. After standing at 0 ° C. for 15 minutes, the mixture was poured into ice-cold 0.5η 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), [<x] _D = + 71.0 ° (c = 1.3 in dioxane), X _max (in ethanol) = 239 ηιμ (ε = 15 580).

Analysis: C ₂₈ H ₃₉ FO ₈ S.

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

b) 21-bromo-9α-fluoΓ-II / 3-hydroxy-16/9-methyl-17 "-valeryloxypregna-1,4-diene-3,20-dione

A solution of 4 g of 9 "-Fluor-II /? - hydroxy-21-methanesulfonyloxy -16/3 - methyl -17" - valeryloxypregnal, 4-diene-3,20-dione in 200 ml of acetone was mixed with 12 g of anhydrous Treated lithium bromide and refluxed the mixture 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), [a] _D = + 99.3 ° (c = 1.6 in dioxane), X _max (in ethanol) = 238 to 239 ηιμ (ε = 16 620 ).

Analysis: C ₂₇ H ₃₆ BrFO ₃ .

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

c) 9α-fluoro-II /? - hydroxy-21-iodo-16 /? - methyl-17 "-valeryloxypregna-1,4-diene-3,20-dione

(1) A solution of 1.66 g of 21-bromo-9 <x-fluoro-

ll ^ -hydroxy-lo ^ -methyl-na-valeryloxypregna-l ^ -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 130 ⁰ C (decomposition), [<x] _D = + 106.2 ° (c = 1.4 in dioxane), λ _ηαχ (in ethanol) = 237 to 239 ηιμ (ε = 16,480) .

Analysis: C ₂₇ H ₃₆ FJO ₅ .

.... calculated C 55.3%, H 6.2 _^0/0) J21,6 ° / _o; found .... C 55.8%, H6.45 ° / ₀ , J21, l ° / o · (2) A solution of 200 mg of 9a-fluoro-II / 3-hydroxy-21-methanesulfonyloxy -16 /? - 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 was refluxed on a steam bath. After 8 days, had about a 75 ° / _o by weight conversion into the 21-iodo compound occurred, as judged from the intensity of the spots in thin layer chromatography.

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

(1) A solution of 50 mg of 9a-fluoro-II / 3-hydroxy-21 -iodine-16/3-methyl-17cv-valeryloxypregna-1,4-diene-3,20-dione in 1.25 ml of pyridine was heated on the steam bath for 3 ^ 2 hours. The mixture was in water poured and extracted with chloroform, and the isolated material (40 mg) was on neutral alumina (Grade IV) chromatographed and yielded after elution with ether and crystallization Benzene-Petroleum 15 mg 9 «-fluoro-II / 3-hydroxy-16/3-methyl-17a-valeryloxypregna-1,4-diene-3,20-dione.

(2) A solution of 300 mg 9 .- <- fluorine-II / 3-hydroxy-21-iodine -1 6β- methyl-17λ-valeryloxypregna -1,4-diene-3.20-dione in 13 ml dioxane was mixed with 10 ml of a 5% aqueous sodium metabisulphite 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, yielding 220 mg of 9A-fluoro-II / 3-hydroxy-16/3-methyl-17A-valeryloxypregna-1,4-diene-3,20-dione; M.p. = 195 ° C, [. \] _D = + 69.2 ° (c = 1.4 in CHCl ₃ ).

Example 3

9A-fluoro-II / 3-hydroxy-16/3-methyl-17a-valeryloxypregna-1,4-diene-3.20-dione

A solution of 500 mg of 9 \ -Fluoro-II / 3-hydroxy-21-methanesulfonyloxy -16/3-methyl-17λ-valeryloxypregna-1.4-3,20-dione in 12.5 ml of pyridine was mixed with 1 g of 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 filtrate gave a further fraction (30 mg) of the product. The combined solids were taken up in acetone and filtered through Florisil (magnesium trisilicate) to remove some of the color and the residue was chromatographed in benzene on 5.5 g of neutral alumina (Grade IV). Elution with ether and double crystallization of the fractions from benzene-petroleum gave 171 mg of 9-fluorine-U / 3-hydroxy-16 / i-methyl-17-valeryloxypregna-1,4-diene-3.20-dicmin in the form of fine needles ; M.p. = 195 to 196 ° C, [λ] /; - 64.9 ° (c - 1.3 in CHCl ₃ ). The infrared spectrum of the product was identical to that of an authentic sample.

Example 4

9α-Fluor-II / S-hydroxy-16/3-methyl-17α-valeΓyloxypregna-l, 4-diene-3,20-dione from 9a-Fluor-II / 3-hydroxy-21-iodo-16jff-methyl- 17 <x-valeryloxypregna-l ₎ 4-dieri-3,20-dione

(a) With pyridine

A solution of 50 mg of 9a-fluoro-II / 3-hydroxy-21-iodine-16/3-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, 9a-fluoro-ll /? - hydroxy-16/3-methyl-17a-valeryloxypregna -1,4-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 heated on the steam bath for 5 hours and then worked up as in Example 4 (a). Crystallization from chloroform-petroleum gave 32.7 mg, corresponding to a yield of 83.5 ° / _0, 9a - fluoro-11/3 - hydroxy -16 / 3- methyl - 17a - valeryloxypregna-l, 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 to give about 5 mg unchanged 21-iodine compound and 24.5 mg, corresponding to 62.5 ° / ₀ yield, 9a-fluoro-ll / 3-hydroxy-16/3-methyl-17a-valerj 'loxypregna-1,4-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-9Ä-fluorII / S-hydroxy-lojö-methyl-na-valeryloxypregna-l ^ -diene-3,20-dione

(a) With sodium iodide in pyridine

A solution of 50 mg of 21-bromo-9, \ - fluoro-II / 3-hydroxy -16/3 - methyl -17. \ - valeryloxypregna -1,4 - diene-3,20-dione and 100 mg of sodium iodide in 2 ml of pyridine was heated on the steam bath for 3 hours. The pyridine was removed in vacuo and the residue filtered in chloroform through a small layer of neutral grade IV alumina. The layer was washed with ether, combined washings and evaporated to give 30 mg, corresponding to 70 ⁰ Z ₀ yield 9. \ - fluoro-ll £ hydroxy-16/3-methyl-17 \ -. Valeryloxypregna-l, 4 -diene-3,20-dione with an infrared spectrum identical to that of an authentic sample.

(b) With sodium iodide in triethylamine

A suspension of 50 mg of 21-bromo-9 "-fluorII / ^ hydroxy - ^ / ^ methyl-nA-valeryloxypregna-l ^ -diene-3.20-dione and 100 mg of sodium iodide in 2 ml of triethylamine was on the steam bath for 8 hours

7 8

heated. The solvent was removed in vacuo. 7 g of methanesulfonate in 200 ml of pyridine were used with

and the residue treated as above to treat 39.6 mg, 14 g of sodium iodide and the mixture

corresponding to 93% yield, 9a-fluoro-II /? - hydroxy- heated on the steam bath for 5 hours. The pyridine

lo / J-methyl-na-valeryloxypregna-l ^ -dien-SjiO-dione was removed in vacuo and the dark, oily

were obtained. Dissolve 5 residue in chloroform and pass through silica gel

, _N ,,. , _T. .,.,. ".. ,,. . filtered. The silica gel was washed with ether 2n, the

(C) Sodium iodide / methylamine-acetone wash waters were evaporated to give a

A solution of 50 mg of 21-bromo-9 «-fluoro-II / 9-hy-yellowish crystalline solid. Crystallization this

droxy -16 /? - methyl -17 «- valeryloxypregna -1,4 - diene material from ether and then from ether - Pe-

3.20-dione and 100 mg of sodium iodide in 1.5 ml of acetone io troleum yielded 2.88 g of 16 /? - methyl-17 «-propionyloxy-

and 1.5 ml of triethylamine was pregna-1,4,9-triene-3,20-dione on the steam bath as silky needles;

Heated for 18 hours. The work-up was done as F. = 177 to 179 ° C, [oc] _D - + 2.7 ° (c = 1.1 dioxane),

described above and resulted in 39.6 mg, corresponding to Xmax (in ethanol) = 237 to 238 ιημ (ε = 15 580).

93% yield, gc-fluoro-ll ^ hydroxy-lo ^ methyl analysis: C ₂₅ H ₃₂ O ₄ .

17 "-valeryloxypregna-1 _; 4-d _{ia-3,20-dione. :} 15 _{;, calculated c} ^ »^ _{R 8> 15%} .-_

Example 6 > ■ - found .... C 75.75%, H 8.1%.

(a) 16 ^ -Methyl-17 «, 21 (l'-ethyl-l'-ethoxymethylene

dioxy) -pregna-1,4,9-triene-3,20-dione Example 7

A solution of 500 mg of 17a, 21-dihydroxy-20 ... (a) 9a-fluoro-II & 21-dihydroxy-16 «-methyl-

16 /? - methylpregna-1,4,9-triene-3,20-dione in 20 ml of di-. 17-propionyloxypregna-1,4-diene-3,20-dione.

oxane was treated with 0.7 ml of triethyl orthopropionate and (dexamethasone-17-propionate)

treated about 5 mg of p-toluenesulfonic acid. After the 5 g of dexamethasone were dissolved in 200 ml of dioxane

Let stand at room temperature for 40 minutes and with 400 mg of p-toluenesulfonic acid and 20 ml of tri

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 then poured into sodium bicarbonate solution. the

16 ö _{i-methyl-17a,} 21- (l'-ethyl-l'-äthoxymethylendioxy) - white precipitate was filtered and dried at 100 ⁰ C

pregna-l, 4,9-triene-3,20-dione dried in the form of cubic and yielded 5.83 g of dexamethasone-17,21-ethyl-

Prisms, m.p. = 175 to 177 ° C, [a] _D = + 5.2 ° (c = 1.0, 30 orthopropionate.

Dioxane), Xmax (in ethanol) = 238 to 239 πιμ This product was dissolved in 240 ml of acetone and

(ε = 16,000). with 48 ml of water and 2.4 ml of 2 η-sulfuric acid

Analvse · CHO sets. The solution was at room temperature

• Allowed to stand for 27 36 ^{seconds for} 30 minutes and then immersed in water .... C 73.6 / ", H 8.25 I ₀ ; _{35 pours; the} p _ro domestic product was isolated with chloroform, geiunden .... C 73.4 / _0, H 8.5 / ". _The crude product was crystallized from acetone-hexane

.,. "" _TT , ",",, "". , sated and gave 3.6g 9a-fluoro-II / ?, 21-dihydroxy-

(b) 21-hydroxy-16 ^ methyl-17 "-propionyloxy-16" -methyl-17-propionyloxypregna-1,4-diene-3,20-dione;

pregna-1,4,9-tnen-3,20-dione _{R = 219 to 22} rc, [<x] _D = -6 ° (c = 1.0 in CHCl ₃ );

Uncrystallized 16 / S-methyl-17a, 21- (l'-ethyl- 4 ° Xmax = 238 ΐημ (EJä, = 351).

l'-ethoxymethylenedioxy) -pregna-l, 4,9-triene-3,20-dione, Analvse · CH FO

that from 8.0 g 17 ", 21-daydroxy-1 ^ -methyl _P regna, calculated""C<57 oo / H7 4" / ·

1,4,9-triene-3,20-dione, as described in Example 6 (a), «erecnnet .... c ο /, υ / ₀ a /, 4 J ₀ ,

was obtained in 95 ml of acetic acid, the 8 ml 'found ... C 67.25 / ₀ , H 7.0 / ₀ .

Contained water, dissolved and _{stored at room temperature 45 / t} _ _{N n} , - ,, _{ΛΛ ο} ,, ^ _1. , _,. ,

Left for 40 minutes. Dilute with water W ^ Huor-ll / y-hydroxy ^ l-methansulfonylo ^ -

and filtration gave the crude product. Crystallization 16'-methyl-17-propionylox _y pregna-1,4-diene-3,20-dione

this product from ether (which contained some acetone) 3 g of dexamethasone-17-propionate were in 30 m

- petroleum gave 7.52 g of 21-hydroxy-16 /? - methyl-pyridine dissolved, and the solution was applied to -1O ⁰ C

17 «-propionyloxypregna-1,4,9-triene-3,20-dione in the form 5 ° chilled. 3 ml of methanesulfonyl chloride were added

of large prisms, F. = 177 to 179 ^o C [<x] z) = + 16.1 ° given and the temperature at about 20 ° C for 30 minutes

(c = 0.9 dioxane), Xmax (in ethanol) = 237 to 238 πιμ held. The reaction mixture was poured into cold,

(ε = 16 210). poured dilute 2 η hydrochloric acid and the white

Analvse · CHO precipitate filtered off and dried (3.3 g). He

• 25 32 ⁵ 'TT τ on / 55 was then crystallized from acetone-hexane and .... Calculated C 72.8%, H 7.8%; _b onate methanesulfonic _29; F. = 183 found to 186 ⁰ C. ... C 73.0 "/", H 7.9%. (Decomposition); [oc) _D = + 46 ° (c = 1.0 in CHCl ₃ );

, .. ,, - ,,,,,., ". , Xmax = 238 ΐημ (Eli = 308).

(c) löp-methyl- ^ a-propionyloxypregna-

l, 4,9-triene-3,20-dione _6o Analysis: C ₂₆ H ₃₅ FO ₈ S.

A solution of 6.7 g of 21-hydroxy-16 /? -Methyl- Calculated .... C 59.3%, H 6.7%, S 6.1%;

17 «-propionyloxypregna-1,4,9-triene-3,20-dione in 50 ml ... c:> y, ö / ₀ , n op / ₀ , & o, i / ₀ .

dry pyridine was at 0 ° with 1.87 ml methane, x «™ ^ -. ot.j -. ^ ^ i

sulfonyl chloride treated. After standing for one hour, ( ^c > 9 " _: fluorine-11, hydroxy-16" -methyl-

at room temperature the mixture was under 65 lT-propionyloxypregna-l ^ -diene-S ^ O-dione

Stir poured into ice-cold η-hydrochloric acid. Filtra- (21-Deoxyd _eX amethasone-17-propionate)

tion resulted in 7.9 g, corresponding to 99% yield, 500 mg 9 <% - Fluor-II /? - hydroxy-21-methanesulfonyl-

21-methanesulfonate as a white amorphous solid. oxy-16α-methyl-17-propionyloxypregna-1,4-diene

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 was crystallized from acetone-hexane to give 140 mg of 21-deoxydexamethasone-17-propionate; m.p. 216-219 ° C; [oc] _D = + 50 ° (c = l in CHCl ₃ ), l _max = 239 ηιμ (Ei * -367).

Analysis: C ₂₅ H ₃₃ FO ₅ .

Calculated .... C 69.3%, H 7.7%; * ⁵

found .... C 69.4 ° / ₀ , H 7.5%.

Claims (1)

Claim: Process for the preparation of 17a-acyloxy-20-ketp-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 the partial structure in position 17 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 ₂ X. CO OCOR CO L- -OCOR
17 ^N. (II) 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.