DE958841C - Process for the preparation of 4, 17 (20) -pregnadiene-11ª ‡ (or 11ª ‰), -21-diol-3-one - Google Patents

Description

The invention relates to a method for the production of new steroids, namely the 4, 17 (2o) -Pregnadien-ii, 2i-diol-3-ones. Those which can be produced by the process according to the invention Connections can be used as intermediate

COO-R

CH

Alkanediol products for the production of bark hormones be used. The method according to the invention was illustrated by the following formulas will:

COO-R

CH

(II)

Lithium aluminum hydride

CH ₂ OH CH

Acid-

in which R, R 'and R "denote hydrogen or alkyl radicals which preferably contain 1 to S carbon atoms inclusive, that is, low molecular weight alkyl groups, w = 0 or 1 and the n-position oxy group shown above has α or / ^ configuration. The novel compounds of the present invention can be represented by the above formula (IV). According to the process of the present invention, a 4,17 (2o) -pregnadiene-3, ii-dione-21 -carboxylic acid ester (I) with an alkane α-diol or an alkane - /? - diol, ie a glycol, in the presence of an acid catalyst with the formation of a 4, I7 (2o) -pregnadiene-3, ii-dioner2i-carboxylic acid ester (II) cyclically ketalized in the 3-position brought together, which is then reacted in the presence of an organic solvent with lithium aluminum hydride, which is followed by a mild hydrolysis of any excess lithium aluminum hydride or organic lithium campex that may be present old, 3-position cyclically ketalized 4,17 (2o) -Pregnaddenrii, 2i-diol-3-ons (III) with aqueous acid gives 4, 17 (2o) -Pregnadienii; 2i-diol-3-one (IV) which are converted into cortisone or 17-oxycorticosterone and their esters (ΠΙ)

can. Acylation of the 21-oxy group carried out in a known manner and introduction of a 17 α-position oxy group with hydrogen peroxide in Gregenwart from osmium tetroxide gives an a-oxycorticosterone acylate. If the 11 β oxy group of the compound (IV) is oxidized after the acylation, but before the introduction of the 17 oxy group, a cortisone-21-acylate is obtained. Both esters can be converted into the free alcohols by mild alkaline hydrolysis in inert solvents.

The compounds represented by the formula (I) can as in 11-graduation oxygen bearing 4, 17 (20) -Pregnadien.-3-one-2i-carboxylic acid esters or as 4, 17 (20) -pregnadien- 3-on-21-carboxylic acids carrying oxygen in 11-S division and their 21-alkyl esters. Accordingly, the compounds represented by the formula (II) can be considered to be in the 3-position cyclically ketalized 4, 17 (20) - pregnadien -3-one-21-carboxylic acid esters carrying oxygen in the ir-position or as cyclically ketalized in 3 * -S division, oxygen-bearing in 11-S division 4, 17 (20) -Pregnadien-3-one-21-carboxylic acids and denote their 21-alkyl esters.

A 4, i7 (2o) -Pregnadien-ii, 2i-diol "3-one, which is represented by the formula (IV), or one of its 21-esters in which the hydroxyl group has a ^ configuration is converted in 4-pregnen- 11 ß, 17 a, 21- triol-3, 20-dione (Kendall's compound F) by converting them to form 4-pregnen-11 ß, 17 a, 20, 21 -tetraol-3 -on-i7, 20-asmiatesters or its 21-ester with osmium tetroxide and these compounds

then z. B. with perchloric acid, its salts or other equivalent oxidizing agents, such as hydrogen peroxide, dialky! peroxy and organic peracids, such as. B. peracetic acid or perbenzoic acid, or potassium dichlorate in a solvent such as an ether or a Alcohol, e.g. B. tertiary butyl alcohol or diethyl ether, oxidized by methods already known (Prins and Reichstein, HeIv. Chim. Acta ,, Vol. 25, 1942, p. 300; Ruzicka and Mueller,

HeIv. Chim. Acta, Vol. 22, 1939, p. 755).

Correspondingly, when using 4, i7 (2o) -Pregnadien-iia, 2i-diol "3-one (IV) as Starting compound and carrying out the same reactions described above and with additional preferential oxidation of the 11-position hydroxyl group to an 11-position keto group, z. B. by esterification of the 21 hydroxyl group in the hydroxylation by osmium tetroxide and subsequent oxidation

tenen 4-Pregnen-iia, 17a, 2i-triol-3, 20-dione and by subsequent oxidation of the 11 terminal hydroxyl group with chromic acid into an 11 position keto group, the 4-Pregnen-17 a, 21-diol-3, ii, 20-trion (Kendall's connectionE).

The 4,17 (20) pregnadiene-3,11-dione-21-carboxylic acid esters used as starting material (I) are made by adding an n-keto ~ 2i, 21-dihalo-21-carbonylprogesterone, which is represented by formula (V),

XXO

C— Γ ¹ "P

C = O c Ii

wherein X is a halogen having an atomic weight of 36 to 127 inclusive, i.e. H. Chlorine, bromine or Iodine, R hydrogen or a. Remainder of the formula

Ii

- ^ C — 0— R '

means, where R 'is a hydrocarbon radical, with a base, such as an alkali metal alcoholate, in the presence of hydroxyl ions or alkoxy ions.

The ketalization is usually carried out at a temperature between about room temperature and the boiling point of the solvent used for about a period of one-half hour up to about 18 hours carried out. If the reaction water is removed at the same time, is the preferred one Reaction time means the time it takes to use about 1 molar equivalent of water per mole of steroid to remove from the reaction mixture. Wepn the parent steroid is a free acid can, under under these circumstances the acid group is formed to some extent by the alkanediol a glycol ester can be esterified. The treatment, the reaction miserable with an alcoholic or aqueous base, preferably an alkali metal base, and the release of the free acid from the salt produced in this way, carefully avoiding hydrolysis of the ketal residue an essentially pure product (II), where R in the 21-position is H, d. i.e. it will be a free one Acid formed.

To! The alkane-a-diols and all an- ß-dioxa that can be used include ethylene glycol, trimethylene glycol and alkyl-substituted ethylene glycols and trimethylene glycols, which preferably contain no more than two alkyl groups as substituents, such as propane-i, 2-diol, butane-i, 2- diol, 3-methylbutane-i, 2-dioli, octane-i, 2-diol, butane-2, 3-diol, pentane-2, 3-diol, 5, 5-dimethyl-octane-2, 3-diol, Butane-1,3-diol, pentane-2,4-diol, 4-methylpentane, 3-diol or octane, -i, 3-diol.

About the acid catalysts which can be used for the reaction belong e.g. B. 'anhydrous hydrochloric acid, concentrated sulfuric acid, para-toluenesulfonic acid, Benzenesulfonic acid or sulfoacetic acid, which must be used at least in traces ..

Solvents that can be used for the reaction include hydrocarbon solvents, halogenated hydrocarbons, ethers or esters, such as benzene, toluene, xylene, hexane, heptane, chloroform, Carbon tetrachloride, chlorobenzene, diethyl ether, dioxane or tetrahydrofuran, or even a Excess of the alkanediol used.

A suitable method for carrying out the reaction described above is that the starting steroid is dissolved in the selected solvent, preferably a water-immiscible solvent such as benzene, toluene or carbon tetrachloride, and the reaction mixture is then heated to its reflux temperature with simultaneous removal of the water formed by the reaction is heated until about 1 molar equivalent of water per mole of steroid has been removed from the mixture. Reaction times of about ¹ hour to several days Zi may sometimes be required to bring the ketalization to a satisfactory extent.

To isolate the ketalized steroid (II) obtained, the reaction mixture is washed with a dilute base, e.g. with dilute

aqueous sodium bicarbonate, sodium carbonate, Potassium hydroxide, methanolic sodium hydroxide or sodium methylate and distilled the Mix then to dryness.

If the solvent used is essentially water-soluble, the washing can be carried out with a base after the solvent has been removed, or the distillation can be replaced by the precipitation of the steroid from the xo mixture by the addition of a large volume of water, which preferably. contains sufficient base to neutralize the catalyst.

The next process stage, ie the treatment of the 4, i7 (2o) -pregnadiene-3, ii-dione-21-carboxylic acid ester (II) obtained, cyclically ketalized in 3-S division, with a reducing agent such as lithium aluminum hydride results a 4, 17 (2o) -Pregnadien-11,2i-diol "3-one (III), which is cyclically ketalized in the 3-position and in which the 11-position hydroxyl group has the α- or / ^ configuration. For reduction with lithium aluminum hydride, a solution of a 4, 17 (20) -pregnadienr 3, ii-dione-21-carboxylic acid ester, which is cyclically ketalized in the 3-position, in an organic solvent which is not reactive under the reaction conditions, becomes a solution or Suspension of. Lithium aluminum hydride given in ether. Other useful solvents are ^1, for example, dioxane or tetrahydrofuran. When using ether, the reaction is usually carried out at a temperature which is between room temperature and the boiling point des.Lc-Sufflgsmittel; however, temperatures can sometimes be successfully used which are substantially below room temperature.

Lithium aluminum hydride is usually used in substantial excess in order to ensure optimum yields of the desired product. When the steroid and lithium aluminum hydride have reacted thoroughly and the heat of reaction has subsided, the reaction is essentially complete. Occasionally, one turns longer. Stir or prolong heating or both to ensure that the reaction is complete. The excess lithium aluminum hydride and possibly formed steroid-Li Al H ₄ complex compounds are decomposed by the careful addition of water to the reaction mixture. If the Reaktionsmisiahung is maintained at an alkaline _pH value, ie, if z. B. no mineral acid has been added during the decomposition of Liithiumaluminiuimhydridsi or thereafter, can 'the Reaction mixture are isolated. The separation of the organic phase from the aqueous phase of the decomposed reaction mixture and the subsequent distilling off of the solvent leaves a 'distillation residue behind which essentially; consists of the desired product. The 4, 17 (2o) -pregnadien-ii, 2i-diol-3-one (III) ketalized in the 3-position can, however, also be reacted further without isolation.

The free 4, 17 (2o) -Pregnadien-ii, 2i-diol-3-one (IV) can be ketalized cyclically in the 3-position by hydrolysis of a solution of the crude or purified 4, 17 (2o) -Pregnadien-ii, 2i-diol-3-ons in an organic solvent with dilute aqueous acid, preferably a mineral acid, such as hydrochloric acid or sulfuric acid, usually, at room temperature and for a period of time from about one Vs hour up to. about 72 hours. The amount of used Acid is usually a trace to a large molar excess. It can be extraordinary diluted to fairly high_ concentrations. be used as the acid only acts as a catalyst for hydrolysis. For the production of 4, 17 (2o) -Pregnad, ienriia, 21-diol-3-one the hydrolysis of the cyclic ketal can take place under rather severe conditions, e.g. B. with a fairly high concentration of the acid and at one well above room temperature lying temperature, while the hydrolysis is preferably at about room temperature and is carried out in the presence of a more dilute acid if the. 4,17 (2o) -Pregnadiene-11 / ?, 2i-diol-3-one should be produced, as the non-permanent hydroxyl group in the presence of a Acid tends to be dehydrated. The reaction time required to complete the hydrolysis and reaction temperature depends to some extent on the particular present in the steroid: 3 permanent Ketal group. Isolation of the free 4, 17 (20) - pregnadia. -11.21-diol-3-ons achieved one expediently by: that onel the reaction mixture · neutralized, the solvent, distilled off or a large volume of water is added, if the solvent is water-soluble is, and then the product so precipitated wins. This requires after drying for the subsequent reactions no purification if the cyclic one used as starting material 3-ketal was pure.

A simple process for the production of a 4, 17 (20) - Pregnadien-11,21-diol-3-one (IV) from 11 o a 4, 17 (20) - Pregnadien - 3, 11-diene -21- acid or one of their alky solid (I) consists in that the starting compound, which is preferably protected in the 3-position by a 3 - ethylene glycol ketal group (II; R 'and R "= H; n = i) , with a reducing agent, e.g. B. lithium aluminum hydride, and then after the decomposition of the complex compound obtained as an intermediate product with water, the 3-position ketal group of the reaction product is generally removed without its isolation.

A preferred embodiment of the invention The process consists of the implementation of the raw material used, 4, 17 (20) -pregnadiene-3 ketalized in the 3-position, ii-dione-2i-acid or its alkyl ester (II)

with lithium aluminum hydride in a water-miscible with reactive solvents such as tetrahydrofuran or dioxane at a temperature which is substantially below room temperature, i.e. H. is at least below 20 °, and the decomposition of the intermediate product obtained in this way Complex compound with water. A low reaction temperature ensures that only one Minimum of. Side reactions occurs and the

ίο Use of a water-miscible solvent guarantees complete contact of the water · with the reactants and avoids a two-phase solvent system. Water is preferred for the decomposition of the complex compound formed, since the steroids in neutral solution are more stable and the decomposition reaction is not affected by the heat of the reaction between lithium aluminum hydride with acid is accompanied. The 3-position ketal group can then by hydrolysis, for example with hydrochloric acid, can be removed without changing the solvent, since that used in the reduction water-immiscible solvent is an excellent solvent for ketal hydrolysis.

The method of the present invention enables the conversion of a steroid with a 4-position unsaturated 3-keto group and a 21-position carboxylic acid ester group into a steroid in which the 21-position carboxylic acid ester group to. a 21-position hydroxyl group has been reduced, while that in 4-position unsaturated 3-keto grouping has remained unchanged. According to previously known methods connect only the keto group or both the keto group and the carboxylic acid ester group, probably with simultaneous saturation of the double bonds in the steroid.

The following examples explain the process according to the invention. For the production of the

4-0 raw materials is used in the context of the present invention Protection not desired.

example 1

3-ethylene glycol ketal of 4,17 (2o) -pregnadiene-3, ι i-dione-21-acid methyl ester

A solution of 5.90 g (0.01 mol) of ii-keto-21,21-dibromo-21-ethoxyoxaly / progesterone was used to prepare the 4, 17 (2o) -pregnadiene-3, ii-dione-21-acid methyl ester 3.24 g (0.06 mol) of commercially available sodium methylate are added in 150 cm ^{3 of methanol.} The mixture obtained was kept at about 25 ° for 3 hours, after which it was diluted with water and extracted twice with methylene chloride. The methylene chloride extracts were dried with anhydrous sodium sulfate, and the solvent was then distilled off at atmospheric pressure. A quantitative yield of 3.60 g of 4,17 (2o) -Pregnadiene-3, n-dioner2i-acid methyl ester remained as an oil. The oil was dissolved in 50 cm ^{3 of} benzene and chromatographed on a column of 170 g of synthetic magnesium silicate (known under the trade name "Florisil"). The column was developed with 400 cm ^{3 of} solvent of the following composition and in the following order: three times with methylene chloride, five times with methylene. chloride + 5% acetone and once with acetone. The eluates obtained on development with methylene chloride + 5% acetone were combined, the solvent was removed from them, and 1.5 g of crystalline methyl 4, 17 (2o) -pregnadiene-3, ii-dione-21-carbonate remained back, which melted ^{at 213 to 214 0} after recrystallization from acetone and hexane hydrocarbons (known under the trade name "SkellysolveB").

Analysis for C ₂₂ H ₂₈ O ₄ :

Calculated C = 74.17; H = 7.92;

found C = 74.37; H = 8.21.

A solution of 1.5 g (0.0042 mol) 4, 17 (2o) -pregnadiene-3, 11-dione -21-carboxylic acid methyl ester in 150 cm ^{3 of} benzene was mixed with 7.5 cm ^{3 of} ethylene glycol and 0.150 g of para-toluenesulfonic acid added and heated to the re-nut temperature of the reaction mixture with stirring for 5.5 hours. The cooled reaction mixture was ^{washed with 100 cm 3 of} a 1% strength aqueous sodium bicarbonate solution. The benzene layer was then poured onto a column of 150 g "Florisil"; the column was developed with 100 cm ^{3 of} solvent in each case - the following composition and sequence: eight times with methylene chloride and three times with methylene chloride + 4% acetone. The methylene chloride uates contained 1.08 g of the 3-ethylene glycol ketal des 4, i7 (2o) - Pregnadiene-3, ii-dione-21-carboxylic acid methyl ester, which, after recrystallization from ethyl acetate ("SkellysolveB"), ^{melted at 188 to 190 0} and showed the analysis below. The eluates obtained with methylene chloride + 4% acetone contained 0.390 g of pure methyl 4, 17 (2o) -pregnadiene-3, ii-dione-21-carboxylate used as starting material. The yield, based on the amount of the converted starting steroid, was 87% of the theoretical amount.

Analysis for C ₂₄ H ₃₂ O ₅ :

Calculated C = 71.94; H - 8.05;

found C = 71.90; H = 7.95

The 3rethylene glycol ketals of other alkyl esters of the 4, 17 (2o) -pregnadiene-

3, 11-dione-21 -carboxylic acid, such as the methyl ester, the Ethyl, propyl, butyl, amyl, hexyl, heptyl or octyl ester, preferably the methyl ester, produced, by adding the relevant alkyl ester of 4,17 (2o) -pregnadiene-3, 11-dione-21-acid the process described in Example 1 in the presence of an acid catalyst, such as anhydrous Hydrochloric acid, bemzenesulphonic acid or para-toluenesulphonic acid, Reacts with ethylene glycol.

One can, the 3-ethylene glycol ketal des

4, 17 (2o) -Pregnadiene-3, 11-dione-21-carboxylic acid methyl ester also produce as follows: After

the method described in Example ι 0.750 g (0.0021 mol) 4, i7 (2o) -Pregnadiene-3, ii-dione-21-carboxylic acid methyl ester for 7 hours in the presence of 0.075 g of para-toluenesulfonic acid with simultaneous removal of the water of reaction with 4 cm ³ Ethylecraglykol implemented in 100 cm ³ benzene. The cooled mixture was washed with cold 2% sodium bicarbonate solution and water; the washed product was extracted with benzene added to the benzene layer. The United. Benzene solutions were dried over sodium sulfate and then poured over a column of 75 g "Florisil". The column was developed with »Skellysolve B« + 5%> acetone. The eluates were collected in fractions of 100 cm ³ each, of which fractions five, six and seven contained 261, 408 and 118 mg of crystalline solids, respectively (together a yield of 93.5%> the theoretical amount). The combined solids were recrystallized from a mixture of 25 cm ³ "Skellysolve B" and 8 cm ³ ethyl acetate which contained 2 drops of pyridine. The first amount of crystalline 3-ethylene glycol ketal of 4, 17 (2o) -pregnadiene-3, ii-diön-21-carboxylic acid methyl ester weighed 0.580 g, melted at 177 to 179 ⁰ and had a rotatability [α] f = + 9 ° in acetone ; a second set of weighed 0.100 g and melted at 165-177 ^0th

3-ethylene glycol ketal des 4, 17 (2o) -pregnadien-11 ß, 2i-diol-3-ones

80 cm ^{3 of} the liquid above a solution of 1 g of lithium aluminum hydride in

100 cm ^{3 of} anhydrous ether were cooled in a flask in an ice bath and treated with 1 g of 3-ethylene glycol ketal des 4, I7 (2o) -Pregnadiene-

3, ii-dione-21-car rxmsäureinethy testers in 50 cm ^{3 of} anhydrous benzene with stirring within 10 minutes. The reaction mixture was then decomposed with a saturated aqueous sodium-potassium tartrate solution, which was carefully added to the reaction mixture. The solvent layer was carefully decanted from the resulting mixture, and the aqueous layer was ^{washed twice with 50 cm 3 of} benzene each time, which was then added to the solvent layer. The combined solvents; solutions were dried over anhydrous sodium sulfate and then poured over a column of 75 g "Florisil". The column was developed with 250 cm ³ solvents of the following composition and sequence: four times with "Skellysolve B" + 10% acetone, six times with "Skellysolve B" + 15% acetone and finally several times with "Skellysolve B" + 25% acetone. The first two "Skellysolve B" + 10% acetone eluates were combined, the solvent was distilled off and the 488 mg solids contained therein were recrystallized from acetone + "Skellysolve B"; they resulted in the 3-ethylene glycol ketal of

4, i7 (2o) -Pregnadien-ii / ?, 2i-diol-3-ons, which at

183-187 ⁰ melted and a rotatory power [a] ² D - - possessed (in acetone) 5 °.

₂₃ H ₃₄ O ₄ :

Analysis for C ₂

Calculated C = 73.76; H = 9.15;

found C = 73.87; H = 9.22.

3-Ethylene glycol ketal des 4, I7 (2o) -Pregnadien-11 a, 2i-diol-3-one

The first "SkellysolveB" + 25% acetone eluate from the chromatographic work-up described above contained 142 mg of the 3-ethylene glycol ketal des 4, i7 (2o) -Pregnadien-iia, 2i-diol-3-one, which was recrystallized from acetone-sSkellysolve B «melted at 206 to 214 ^0.

Correspondingly, the 3-ethylene glycol ketals of 4,17 (2o) -pregnadiene-Iia, 2i- and τ τβ, 21-diol-3-ons are converted into ether with the 3-ethylene glycol ketal of 4, 17 (2o) - Pregnadiene-3, 11-dione-21-carboxylic acid or one of its alkyl esters, such as the methyl, ethyl, propyl, butyl, isobutyl, amyl, hexyl, heptyl or octyl ester.

4, 17 (2o) -Pregnadien-ii α, 2i-diol-3-one

A solution of 2.4 g (0.0642 mol) of the 3-ethylene glycol ketal des 4, I7 (2o) -Pregnadien-11α, 2i-diol-3 "Ons in 160 cm ^{3 of} acetone was mixed with 4 drops of concentrated sulfuric acid in 40 cm ^{3 of} water were added, and the mixture was refluxed for 2 hours. The cooled solution was neutralized by the addition of a dilute aqueous sodium bicarbonate solution, then the acetone was removed by distillation under reduced pressure. The precipitated product was extracted with methylene chloride, which after The dried methylene chloride solution was distilled to dryness under reduced pressure to leave a residue of 1.96 g (93% of the theoretical yield) of a product consisting essentially of 4,17 (2o) -Pregnadien-iia, 2i-diol "3-one consisted of.

4, 17 (2o) -Pregnadien-ii ß, 2i-d; iol-3-one.

A solution of 0.572 g (0.0015 mol) of the 3-ethylene glycol ketal des 4, I7 (2o) -Pregnadien-11 / S, 2i-diol-3-one in 40 cm ^{3 of} acetone was mixed with water to a volume of 50 cm ³ diluted; then eight drops of concentrated sulfuric acid were added; thereafter the reaction mixture was kept at room temperature for 24 hours. The reaction mixture was then made alkaline by the addition of a saturated aqueous sodium bicarbonate solution; the acetone was then evaporated from the mixture. Then methylene chloride and more water were added; the methylene chloride layer was removed and the solvent was distilled off. After this

Drying in vacuo consisted of the residue from the theoretically expected 0.518 g of 4, i7 (2o) -Pregnadien-II ß, 2i-diol-3-one.

Recrystallization of this product from ethyl acetate "Skellysolve B" gave crystals of 4, i7 (2o) -Pregnadien-ii / I, 2i-diol-3-one, which ^{melted at 156 to 158 0} and a rotatability [a] ² I = + 128 ° (in acetone).

Analysis for C ₂₁ H ₃₀ O ₃ :

Calculated C = 76.32; H = 9.15;

found C = 76.04; H = 9.43; "

C = 75.83; H = 9.40.

Using the method described above, other 3-ketals of 4,17 (2o) -Pregna-r dien-ii ß, 2i-diol-3-one or 4, 17 (2o) -Pregnadiene-ΐΐα, 2i- diol-3-ons can be converted into the free 3-ketones with a hydrolyzing agent such as dilute hydrochloric acid or sulfuric acid.

Example 2

3-Trimethylene glycol ketal of 4,17 (2o) -Pregnadiene-3, ii-dione-21-carboxylic acid methyl ester
f

According to the method described in Example 1, the conversion of 4, 17 (2o) -pregnadiene-3, ii-dione-21-carboxylic acid methyl ester with Trimethylene glycol in the presence of a. Acid catalyst the 3-trimethylene glycol ketal of 4, i7 (2o) -pregnadiene-3, ii-dione-21-carboxylic acid meth.yles.ter.

Similarly, other 3-ketals become this one Esters and other esters of 4,17 (20) -Pregnadiene-3i 11-dione-21-carboxylic acid by the reaction of a selected esters of said steroid acid, especially methyl, ethyl, propyl, butyl, Amyl, hexyl, heptyl or octyl ester, with a Glycol, such as ethylene glycol, propylene glycol, trimethylene glycol, alkyl-substituted ethylene glycol, Propylene glycol or trimethylene glycol, in the presence of an acid catalyst such as para-toluenesulfonic acid, Hydrochloric acid or sulfuric acid.

3-Trimethylene glycol ketal of 4,17 (2o) -Pregnadien-11α, 21- and 11β ] 2i-diol-3-one

The implementation of the 3-trimethylene glycol ketal of 4, 17 (2o) -Pregnadiene-3, 11-dione-2 i-carboxylic acid methyl ester with lithium aluminum hydride in tetrahydrofuran gives the 3-trimethylene glycol ketals des 4, 17 (2o) -Pregnadien-iia, 21- and 11 / ?, 2i-diol-3-ons, also by the implementation other alkyl esters of the 3-trimethylene glycol ketal of 4, i7 (2o) -pregnadiene-3, 11-dione-21-carboxylic acid can be produced.

Other cyclic 3-ketals des 4, I7 (2o) -pregnadiene-ii, 2i-diol-3-ons in which the 11 permanent

Hydroxyl group has α- or ^ -configuration, v / grounding by reacting a selected cyclic; 3-ketals of 4, I7 (2o) -pregnadiene-3, 11-dione-21-carboxylic acid or one of its alkyl esters, e.g. B. with an alkali metal aluminum hydride produced, the cyclic 3-position ketal group of the 'cyclic' prepared in this way 3-Keitalsi des 4,17 (2o) -Pregnadien-ii, 2i-diol-3-ones • and the reduced product are the same. The cyclic 3-ketals in, the starting compounds and may be present in the compounds obtained include e.g. B. Ethylene ^ glycol ketal, propylene glycol ketal, trimethylene glycol ketal, butane-1,2-diol ketal or hexane-3, 4-diol-ketal.

Claims (3)

PATENT CLAIMS: i. Process for the preparation of 4, 17 (20) -pregnadiene, -11 α (or 11 ß), 21-diol-3-one, characterized in that the 4, 17 (20) -pregnadiene-3,11- dian-21-carboxylic acid or its · alkyl esters, those of the formula COOR and in which R is hydrogen or an alkyl radical, in a known manner with an alkane ^ a-diol or an alkane / 9-diol in the presence of an acid catalyst, the 3-ketal obtained in known Way reduced in the presence of an organic solvent with lithium aluminum hydride and the obtained 4, i7 (2o) -Pregnadien-iia (or 11 /?), 2i-diol-3-one-3-ketal in known Way hydrolyzed acidic. 2. The method according to claim 1, characterized in that that one uses ethylene glycol as a ketalizing agent. 3. The method according to claim 1 and 2, characterized in that 4.17 (2o) -pregnadiene-3, ii-dione ~ 2i-carboxylic acid methyl ester "as the starting compound used. Considered publications:
U.S. Patent Nos. 2356154, 2378918; Ber. d. German former Ges., Vol. 71, 1938, p. 1766; Journ.Amer.Chem.Soc., Vol. 71, 1949, p. 756; Vol. 72, 1950, p. 367; Chimia, Vol. 5, 1951, p. 25. © 609 616/492 8.56 (609 809 2. 57)