DE2909433A1 - Anti:gestagenic 15-beta, 17-beta-methylene:oxy steroid derivs. - prepd. by cyclisation of 15-beta-halomethyl-17-beta-hydroxy-steroid(s) with strong base - Google Patents

Abstract

New 15 beta, 17 beta-methylenoxy steroid are cpds. of formula (I): (where R1 is H or CH3 when there is a single bond in the 5,10-position; R2 is CH3 or C2H5; R3 is H or an opt. substd opt. unsaturated lower hydrocarbon residue; X is OXo, 2-6C alkylenedioxy, o-phenylenedioxy or H, OR4, R4 is H, lower alkanoyl or tetrahydropyranyl; and is a double bond in the 4,5-, 5,6- or 5,10 position). (I) have a strong affinity for the gestagen receptor, from which they displace progeoterone, and are devoid of progestative activity. (I) can thus be used as antigestagens for the induction of abortions.

Description

Ί 5ft ιI7ß-Mothylonoxy-Stcroidc.

Process for their production and pharmaceutical preparations containing them

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ί ■ "

f .;

tr:

f The invention relates to 15ß, 17ß-Methylenoxy-Stcroids,

Process for their preparation and containing these steroids pharmaceutical preparations.

• / j It has been found that the new 15ß, 17ß-methylenoxy-

Steroids have a strong affinity for the progestin receptor. They displace progesterone from the receptor and can thus prevent the effects of progesterone. The new 15ß »17ß-Methylenoxy-steroids show no progestative Effect and are therefore suitable as antigestagens to trigger abortions.

The steroids of the general formula I according to claim 1 can be unsubstituted in the 17ct position (R_ = H) or as substituents R- a substituted or unsubstituted, saturated or unsaturated lower hydrocarbon bear rest. Such lower hydrocarbon radicals are, for example, alkyl radicals with 1-5 carbon atoms, preferably the methyl and ethyl radicals, alkenyl and alkynyl radicals with 2-3 carbon atoms, preferably the vinyl, ethynyl and propynyl radicals. The hydrocarbon residue can also be used in a suitable manner by an or several hydroxyl groups or halogen atoms may be substituted, the chloroethynyl radical being substituted Hydrocarbon radical is preferred.

A lower alkanoyl group R ^ should preferably be 1-8 Contain carbon tomo. Suitable alkanoyl groups Ri are for example the formyl, acetyl, propionyl, Butyryl, isobutyryl, trimethylacetyl, pentanoyl, hexanoyl, heptanoyl and octanoyl groups.

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The new 15ß »17ß-methylenoxy steroids of the general Formula I according to claim 1 are according to the invention produced by the method according to claim 12.

The process characterized in claim 12 takes place under the conditions of the elimination of hydrogen halide. According to the present invention, strong anhydrous bases in polar ones are used as hydrogen halide-releasing agents aprotic solvents are particularly suitable. Such strong bases are, for example, alkali metal alcoholates, Alkali metal amides and alkali metal hydrides, such as potassium tert-butoxide, potassium or sodium isopropoxide, Potassium, sodium or lithium ethylate, sodium amide, sodium hydride etc., with potassium tert-butoxide being preferred. The elimination of hydrogen halide occurs in a polar aprotic Solvent, such as dimethyl sulfoxide or dimethylformamide, made, optionally in Presence of other inert solvents such as tetrahydrofuran, dioxane, etc. The reaction is usually carried out at a temperature between -20 C and +50 C, preferably at room temperature.

17oc ~ Standing alkynyl groups can subsequently be added if desired converted in a manner known per se into the corresponding 1α-alkenyl or 17α-alkyl groups by llydxing Air earths. As is known, this hydrogenation is preferably carried out in such a way that the 17 <x -alkynyl steroids are mixed with Reacts hydrogen in the presence of a hydrogenation catalyst. As hydrogenation catalysts, for example Palladium catalysts or platinum oxide catalysts, optionally on supports, can be used.

Is used as starting compounds of the invention Method 3-ketals (Y = one 2-6 carbon atoms containing alkylenedioxy group or an o-phenylenedioxy group) of the general formula II, the obtained

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• · O

_ ₃ _ 2903433

Ketals in a manner known per se with v.-aqueous acids be hydrolyzed.

In addition, further counter-measure measures may apply connect to the halogen water separation.

A 3-tetrahydropyranyloxy group can be replaced by acid Hydrolysis can be converted into the 3-hydroxy group. For example, the 3-tetrahydropyranyloxysteroid hydrolyzed in methanol and water in the presence of an acid, expediently in the presence of oxalic acid at the boiling point.

5 k '

The oxidation of the 3-hydroxy-A compound to the 3-keto-A compound takes place according to methods known per se. For example, you can use the 3-hydroxysteroid with a Oxidize aluminum alcoholate in the presence of a ketone. For this oxidation known under the name Oppenauer is, one preferably uses aluminum alcoholates of secondary or tertiary alcohols, such as, for example Aluminum isopropoxide, aluminum tert-butoxide or Aluminum phenolate, and lower aliphatic or isocyclic ketones such as acetone, methyl ethyl ketone, cyclopentanone or cyclohexanone. In the case of the Oppenauer oxidation, any one that may be present in the starting material

5 k '

Δ double bond rearranged into a Δ double bond.

The oxidation of the 3-hydroxy-A compound to the 3-keto-A compound is also carried out in the usual way, preferably with 2,3-dichloro-5,6-dicyanobenzoquinone in Dioxane or with manganese dioxide in chloroform, each at room temperature.

For the esterification of the 3-hydroxyl group, steroidal alcohols are usually esterified in steroid chemistry applied procedure in question. For example

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the implementation dos 3-Uyd * "o :: yatcroidn tn. '. t
an acid anhydride or shurcholoccnide in the presence
a tertiary amine such as pyridine, 'i-dimethylaminopyridine, collidine or triethylamine
Room temperature. The 3-hydroxysteroid can also be used with the
desired acid anhydride can be esterified using a strong acid such as p-toluenesulfonic acid or with the corresponding acid and trifluoroacetic anhydride at room temperature. .j

The according to the method according to the invention according to claim 12. j

used starting compounds of the general formula II j

can in a manner known per se from the corresponding ']

15ß | i6ß-methyl steroids by Halogenwasserstoffanla- Λ

ge tion and introduction of R- in 17oc position obtained i

will. \

15β1 oss methylene steroids are described in US Pat
German patents 1,593,501, 1,643,050, in the
German Offonlegingsschrift 2 k ^ S Ο68 and in the
U.S. Patent 3 ^ 70 16Ο.

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«I ft · 'Q * * ·· · · C

Preparation of the starting compounds of the general formula II

A: 15β-Chloromethyl-18-methyl-3, 3 (2 ', 2' * -dimethyl-propylenedioxy) -5 and 5 (iO) -estren-17β-ol

11 g of 18-methyl-15β | 16β-methylene-3,3 (2 ', 2'-dimothylpropylenedioxy) -5 and 5 (iO) -estren-17-one (German Offenlegungsschrift 2 ^ 56 068) are dissolved in 110 ml of acetic acid dissolved, saturated with dry hydrogen chloride while cooling with ice and then left to stand for 17 hours at room temperature. It is then stirred into ice water, the filtered precipitate is taken up in methylene chloride and washed successively with water, sodium hydrogen carbonate solution and water. After drying and evaporation, the residue is chromatographed on silica gel and, recrystallized from diisopropyl ether / acetone, 4.3 g of 15β-chloromethyl-1B-methyl-il-ostrene-3,17-dione with a melting point of 180-182 ° C received. .UV: C ₂₃₉ η 17 600.

3i7 g of 15β-chloromethyl-i8-methyl - ^ - oestrene-3,17-dione are warmed to 50 ° C. in 27.7 tnl methylene chloride, successively with 7i ^ ml of triethyl o-formate, 11.1 g of 2,2-dimethyl 1,3-propanediol and 37 mg of p-toluene sulfonic acid were added and the mixture was stirred at 50 ° C. for 15 minutes. It is then diluted with ether, washed with sodium hydrogen carbonate solution and water, dried over sodium sulfate and evaporated to dryness in vacuo. After chromatography on Siiikagol, 4.5 g of 15β-chloromethyl-18-methyl-3,3 (2 ^l , 2'-dimethyl-propylenedioxy) -5 and 5 (10) -estren-17-one are obtained as an oil.

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• ·

• 1 I.

1.5 g Lithium titrated butoxyalanate is added and the mixture is stirred at room temperature for 30 minutes. It is diluted with ether, washed with potassium-sodium tartrate solution and water, dried and evaporated. 15 g of 15β-chloromethyl-18-niethyl-3 _> 3 (2 ', 2'-dimethylpropylenedioxy) -5 and *> (i0) -östren-17β-ol are obtained as an oil *

B: 17 <x -ethynyl-15β-iodomethyl-18-methyl-3,3 (2 ', 2' -dimethyl propylenedioxy) -5 and 5 (iO) -östren-17ß-ol

20.0 g of 18-methyl-15ßii6ß-methylene-3,3 (2 ', 2'-dimethylpropylenedioxy) -5 and 5 (10) -estren-17-one are dissolved in 200 ml of formic acid with 60 g of potassium iodide for 2k hours at room temperature touched. It is then precipitated in ice water, the filtered precipitate is taken up in methylene chloride and washed successively with water, sodium thiosulfate solution, water, sodium hydrogen carbonate solution and water. After drying and evaporation, 22 g of 15β-iodomethyli8-methyl-4-estren-3,17-dione are obtained as an oil. UV: C ₂₃₉ = 16,100.

22 g of IJß-iodomethyl-iß-methyl-'l-oestrene-S, 17-dione verden in 220 ml of methylene chloride with kk ml of o-formic acid triethyl ester, 66 g of 2,2-dimethyl-1,3-propanediol and 220 mg p-Toluenesulfonic acid was stirred at 50 ° C. for 2 hours. It is then diluted with ether, washed with sodium hydrogen carbonate solution and water, dried and evaporated in vacuo. The residue is chromatographed on silica gel, and 16.8 g of 15β-iodomethyl-18-methyl-3,3 (2 ', 2'-dimethyl-propylenedioxy) -5 and 5dO) -estren-17-one are obtained as an oil .

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8.0 g of magnesium turnings were converted into ethyl magnesium bromide in 120 ml of TILF with 35 nl of ethyl bromide. The solution is added dropwise to 330 ml of absolute THF saturated with acetylene while cooling with ice. 16 g of 15β-iodomethyl-1 8-methyl-3,3 (2 ', 2'-dimethyl-p * pylenedioxy) -5 and 5 (10) -estren-17-one, dissolved in 85 ml of absolute THF was added dropwise and stirred for 20 hours at room temperature. The excess reagent is then mixed with saturated ammonium chloride solution while cooling with ice. After extraction with ether and drying, the residue obtained after evaporation is chromatographed on silica gel. 14.5 g of 17oc-ethynyl-15β-iodomethyl-1 8-methyl-3- _t 3- (2 ', 2'-dimethyl-propylenedioxy) -5 and 5 (10) -estren-17β-ol are obtained as an oil obtain.

C: 15β-Iodomethyl-17α, 18-diethyl-3,3 (2 ¹ ^ ¹ -dimethylpropylenedioxy) -5 and 5 (1 °) -estren-17β-ol

5 «0 g of magnesium shavings are dissolved in 18C ml of absolute THF reacted with methyl bromide. With ice cooling, 10 g of 15β-iodomethyl-18-methyl-3,3 (2 ', 2'-dimethyl-propylenedioxy) -5 are then added to this solution and 5 (i0) -estren-17-one in 180 ml of absolute THF and 3.5 hours stirred at room temperature. With ice cooling then the excess reagent with saturated ammonium chloride solution decomposed and the aqueous phase extracted with ether. After drying and evaporation 9.5 g of 15β-iodomethyl-17a, 18-dimethyl-3,3 (2 ', 2' ■ dimethyl-propylenedioxy) -5 and 5 (10) -estren-17β-ol obtain.

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D: 15β-Iodomothyl-3β- (tctrnhyoropyi-nn-2-yloxy) -5-cndrcntcm-17Λ-Ο1

15β, 16β-methylon-5-indronten-17-one

(US patent 3 'ί? Ο ΐ6θ) was under ice cooling in 90 nl
Acetic anhydride is added to formic acid over a period of 2 hours, and the mixture is stirred for a further 3 hours while cooling. After ice water precipitation, the precipitate becomes
filtered off, taken up in methylene chloride, with '..

Natriumhydrogcncarbonatlösung and water,] \ dried and evaporated. It becomes 9 | ß g raw
3ß-Formyloxy-15ß, 16ß-methylen-5-andro sten-17-one
obtain.

9.8 g of crude 3ß-formyloxy-15ß, iGß-methylene-1-androstene- | i

17-on are in 98 ml of formic acid with 29, ^ g of potassium \\

iodide stirred for 17 hours at room temperature. According to Eis- j:

water precipitation, the precipitate is filtered off, in ji

Mothylene chloride added, with sodium thiosulphate / | solution and water washed and dried. After this

12.0 g of crude 3β-formyloxy-15β-k are evaporated

iodomethyl-5-androsten-1 7-one obtained. \ j

12 g of crude 3β-formyloxy-15β-iodomethyl-5-androsten-17-one
are stirred in 200 ml of methanol with 6 ml of concentrated hydrochloric acid for 2 hours at room temperature. After ice water precipitation, the precipitate is filtered off, taken up in Ί methylene chloride, washed with sodium hydrogen carbonate solution and water and dried. It ;; 12 g of crude 3β-hydroxy-15β-iodomethyl-5-nndrosten- j 17-one are obtained. '■

12 g of crude 3ß-hydroxy-15ß-iodomethyl-5-androsten-17-one.!

are in 120 ml of absolute TIIF with 12 ml of 3, "- Dihydro- ijj

211-pyran and 3 drops of phosphorus oxychloride added and I,

Stirred for 75 minutes at room temperature. It will then;

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prediluted with ether, with anhydrous hydrogen carbonate solution and what you want, dried and evaporated. The residue is chromatographed in silica gel, and 12.2 g of 15β-iodomethyl-3β- (tetr / «hydropyran-2-yloxy) -5-androstene-1 7-on received.

11.6 g of 15β-iodomethyl-3β- (tetrahydropyran-2-yloxy) -5-andlrosten-17-one are bfei in 1l6 ml of absolute THF with 11.6 g of lithium tri-tert-butoxyalanate for 1 hour Room temperature stirred. It is then diluted with ether, with potassium sodium tartrate solution and water washed, dried and evaporated. 11.1 g of 15β- «iodomethyl ~ 3β- (tetrahydropyran ^ - -i 7ß-ol obtained.

15β-chloromethyl-18-methyl-'l-bstren-3β, 17β-diol

3.0 g of 15β-chloromethyl-i8-methyl - ^ - oestren-3,17-dione (prepared according to A) are mixed with 4.5 g of lithium tri-tert-butoxyalanate in 30 ml of anhydrous tetrahydrofuran and added for k hours Room temperature stirred. It is then diluted with ether and washed with saturated potassium sodium tartrate solution and water. After drying and evaporation, 3.05 g of ISβ-chloromethyl-iG are obtained
obtained diol as a crude product.

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example 1 Example 2

To 12.4 g of 17α-ethynyl-15β-iodomethyl-18-methyl-3,3 (2 ', 2'-dimethyl-propylenedioxy) 5 and 5 (10) -estren-17β-ol becomes one Added a solution of 12.4 g of potassium tert-butoxide in 500 ml of DMSO and stirred for 45 minutes at room temperature. It will then stirred in ice water, extracted with ether and, after drying and evaporation, the residue becomes on Chromatographed silica gel. 6.2 g of 17oc-ethynyl-18-methyl-15β, 17β-methylenoxy-3,3- (2 ', 2 · -dimethyl-propylenedioxy) -i4 {: - oestra-5 and 5 (i0) -en obtained as an oil.

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7.4 g of 15β-chloromethyl-i8-methyl-3,3 (2 ', 2 ¹ -dimethylpropylenedioxy) -5 and 5 (1O) -estren-17β-ol are mixed with a solution of 14.8 g of potassium under argon. tert-butoxide in 185 ml of dimethyl sulfoxide (DMSO) was added and the mixture was stirred at room temperature for 1.5 hours. After ice water precipitation, the filtered precipitate is taken up in ether, washed with water and dried. After evaporation, the residue is chromatographed on silica gel, and 3.2 g of 18-methyl-15β, 17β-methylenoxy-3,3 (2 ', 2'-dimethyl-propylenedioxy) -i4§ -östra-5 are obtained and 5 (iO) -eri obtained.

A recrystallized from diisopropyl sample melts at 186 to 187 ⁰ C.

3.0 g of 18-methyl-15β, 17β-methylenoxy-3,3 (2 ', 2'-dimethylpropylenedioxy) -i4f-oestra-5 and 5 (i °) -en are dissolved in 60 ml of methanol with 3 | 0 ml 8 vol./iiger sulfuric acid stirred at 6O C for 1 hour. After dilution with ether, it is washed neutral with B water, dried and evaporated. The residue is chromatographed on silica gel, and 1.6 g of 18-methyl-15β, 17β-methylenoxy-14f-oestra-4-en-3-one with a melting point of 134 ° -34.5 ° C. are recrystallized from diisopropyl ether. UV: ε _24ο = 15 600.

2908433

3iO g of 17a-ethynyl-iO-methyl-15ß, 17ß-methylcnoxy-3,3 (2 ', 2 · - dimethyl-propylenedioxy) -1Ίξ-oestrn-5 and 5 (iO) -cn are in 75 ml of methanol with 3 , 0 ml of 8% sulfuric acid stirred for 3 hours at room temperature. It is diluted with ether, washed with water and dried. After evaporation, the residue is chromatographed on silica gel, and 1.2 g of 17α-ethynyl-18-methyl-15β, 17β-methylenoxy-i'l £ -östra-4-en-3 are recrystallized from diisopropyl ether / acetone -on obtained from melting point 192 - 193 ° C. UV: e _24o = 17 500.

\ Example 3

1.0 g of 17c £ -ethynyl-18-methyl-15β, 17β _r methylenoxy-3, 3 (2 ', 2'-dimethyl-propylenedioxy) -1 ^ l-oestra-5 and 5 (iO) -ene hydrogenated in 80 ml of benzene with 500 mg of Lindlor catalyst (Pd-CaCO-PbO) until one equivalent of hydrogen is absorbed. The catalyst is filtered off and evaporated to dryness in vacuo. 1.0 g of crude 18-methyl-15β, 17β-methylenoxy-3,3 (2 ', 2 ■ -dimethyl-propylenedioxy) -17avinyl-1'i | -estra-5 and 5 (10) -en are obtained .

1.0 g of crude 18-methyl-15β _t 17β-methylenoxy-3,3 (2 ', 2 ¹ -dimethyl-propylenedioxy) -1 7a-vinyl-1 ^/ 1 ^ -estra-5 and 5 (10) -ene are stirred in 20 ml of methanol with 1 ml of 8% heavy silicic acid for 3 hours at room temperature. It is then diluted with ether, washed with water, dried and evaporated. The residue is chromatographed on silica gel, and 180 mg of 18-methyl-15 [beta], 17 [beta] -methyleneoxy-17-vinyl-i'i | -östra-'l-en-3-one are obtained.
UV: C ₂₃₉ = 16,800.

03C038 / 0260

til

t

· ■ β

- 12 -

example

1.0 g of 17α-ethynyl-18-methyl-15β, 17β-methylcnoxy-3,3 (2 ', 2'-dimethyl-propylcndioxy) -1 * »£ -östra-5 and 5 (iO) -cn are in

00 ml benzene with 1 g Lindlar catalyst until uptake of two equivalents! Hydrogenated hydrogen. It will be like in Example 3 described worked up, and there are 1.0g Crude 17a-ethyl-18-methyl-15ß, 17ß-methylenoxy-3,3 (2 ', 2'-dimethyl-propylenedioxy) -i4 ^ -estra-5 and 5 (iO) -s obtained

1.0 g of crude 17 ”r-ethyl-18-methyl-15 [beta], 17 [beta] -methyleneoxy-3, 3 (2 ·, 2'-diraethyl-propylenedioxy) -i4 | -östra-5 and 5 (10) -en are subjected to the ketal cleavage as described in Example 3. After chromatography, 250 mg

17oc-Ethyl-1 8-methyl-15 [beta], 17 [beta] -methyleneoxy-1 4 | -östra-Ί-βη-3-one obtain.

UV: c _2k0 = 17,000.

Example 5 ij

- - si

9.5 g of crude 15β-iodine methyl-17cc, 18-dimethyl-3, 3 (2 ', 2 ¹ -di-ij

methyl-propylenedioxy) -5 and 5 (10) -östren-17ß-ol are in $

ti 95 "Ι absolute THF and added to a solution of 19 ς ϊ \ potassium tert-butoxide in 190 mL DMSO was added dropwise. After one hour at room temperature, the reaction solution is stirred into Eiswaaser, extracted with ether and dried.

The residue obtained after evaporation is at SiIi- _ä \ kagcl chromatographed, and there will be 2.7 S 17oc, i8-di- 'I methyl-15SS, 17-methyleneoxy-3,3 (2', 2 · dimethyl propylenedioxyJ-i'if-cotra-S and 5 (i0) -en obtained.

2.6 g of 17o, 18-dimethyl-15β, 17β-methylenedxy-3,3 (2 ^I , 2 »-dimethyl-propylcndioxy) -i'i & -östrn-5 and 5 (10) -one are dissolved in 26 ml of hfethanol with 2 , 6 ml 8 vol. Fig sulfuric acid stirred for 2 hours at room temperature. It is then diluted with ether, washed with water, dried and evaporated. After chromatography on silica gel,

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• ♦ · «I · ■

- 13 -

crystallized from diisopropyl ether / acetone, 250 mg

I 17o, 18-dimethyl-15β, 17β-methylenoxy-14f-oestra-4-en-3-one

h with a melting point of 163.5-165 ° C.

* "· ■ = 17 100.

Example 6

11.1 g 15ß- "iodomethyl 3ß- (tetrahydropyran ^ -yloxyi - ^ - ^ ß androstene-ol tert potassium in 222 ml of absolute THF under cooling with ice, 11.1 g _1.-Butoxide in 222 nil DMSO

added, and stirring is continued for 45 minutes while cooling. It is then precipitated in ice water, the precipitate is filtered off, taken up in methylene chloride and gelatinized with water to wash. After drying and evaporation, the back -'- < stood chromatographed on silica gel. 1.1 g of 15 [beta] 17 [beta] -methyleneoxy-3 [beta] are recrystallized from diisopropyl ether (tetrahydropyran-2-yloxy) -14 & -androst-5-en from the enamel

I point 137-138.5 ° C obtained.

f Example 7

[*; 1.2 g of 15β, 17β-methylenoxy-3- (tatrahydropyran-2-yloxy) -

II 14 | -androst-5-en are dissolved in 24 ml of methanol and 2.4 ml

& Water with 1.25 g of oxalic acid under reflux for 1.5 hours

ir- heated. It is diluted with ether and washed with water

| ^: ; and dried. After evaporation, 1.1 g become crude

^! 0 15β »17β-methylenoxy-14 | -androst-5-en-3β-ol obtained.

Example 8

\ 1.1 g 15SS »17-methyleneoxy i4 | androst-5-en-3.beta.-ol

! in 22 ml of toluene and 2.2 ml of cyclohexanone with 220 mg of aluminum

nium isopropoxide in 5 ml of toluene and 45 minutes heated while slowly distilling off. It is then diluted with ether, with dilute sulfuric acid and water gownnchen, dried and evaporated. The residue is chromatographed on silica gel. After recrystallization

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510 mg of 15β, 17β-methylenoxy-i'i ^ -androst-'i-en-3-one with a melting point of 170-179.5 ° C. are obtained from diisopropyl ether / acetone.
UV: ε ₂₃₉ = 15,500.

Example 9

I ₁ O g 15SS-chloromethyl-18-methyl-4-estrene-3ß, 17ß-didl in 40 ml of DMSO with 2.0 g of potassium tert-butoxide for 3 hours at room temperature. It is then stirred into ice water, extracted with ether, the organic phase washed with water, dried and evaporated. 750 mg of crude 18-methyl-15 [beta], 17 [beta] -methylene oxy-14 | -estra-4-en-3 [beta] -ol are obtained.

Example 10

750 mg of crude 1 8-methyl-15ß, 1 7ß-methylenoxy-i'if-oestra-4-en-3ß-ol are dissolved in 7.5 ml of dioxane with 750 mg of 2,3-dichloro-5,6-dicyan p-benzoquinone is stirred for 2 hours at room temperature. It is diluted with ether, washed with sodium hydrogen carbonate solution and water, dried and evaporated. The residue is chromatographed on silica gel. After recrystallization from diisopropyl ether, k ^ 0 mg of 18-methyl-15 [beta], 17 [beta] -methyleneoxy-14E-estra-4-en-3-one with a melting point of 133-13 ° C. are obtained. = 15,300.

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Claims (12)

Claims R. a hydrogen atom or a methyl group if there is a single bond in the 5 »10 position, R "a methyl or ethyl group, R. a hydrogen atom or a substituted or unsubstituted, saturated or unsaturated lower hydrocarbon rust, an oxo group containing 2-6 carbon atoms Alkylenedioxy group or o-phenylenedioxy group or the grouping H, ORy, where R. is a Hydrogen atom, a lower alkanoyl or a Represents tetrahydropyranyl group, and a double bond in 'i, 5- » position 5.6- or 5.10- mean. 030038/0260 2303433 2. ) iO ~ methyl-13β, 17β- "iothylcnoxy-1l 3.) 1 7a-Ef..inyl-1 0-methyl- 1 5fi, 1 7ß-ncthylenoxy- 1 k% -östrn-Ί-οη-3-οη. k.) 18-methyl-5ß 1, 1 7.beta.-me thylenoxy-17a-vinyl-1 k% -estr d-en-3-one. 5 ·) 17o-ethyl-1ß-methyl-1 5ß, 1? Ss-methylenoxy-1 4 | -ös tra- 6.) 17a, 18-dimethyl-15β, 17β-methylenoxy-14j -oatra-4-en-3-one. 7 ·) 150i17ß-methylenoxy-3ß- (tetrahydropyran-2'-yloxy) -i4 | -androst-5-en. 8.) 15β.17β-methylenoxy-14 | -androst-5-en-3β-ol. 9 ·) 15 [beta] »17 [beta] -methyleneoxy-1 ^/ t | -androst- ^/ l-en-3-one. 10.) 18-Methyl-15β, 17n-methylenoxy-14 | -estra-4-cn-3β-ol. 11 ·) Pharmaceutical preparations characterized by a Content of a compound according to claims 1-10. 12.) Process for the preparation of 15ß, 17ß-methylenoxy steroids of the general formula I. (D, J30038 / 0260 2903433 wherein R _{1 is} a hydrogen atom or a methyl group if there is a single bond in the 5 (iO) position, R "a methyl or ethyl group, R- is a hydrogen atom or a substituted one or unsubstituted, saturated or unsaturated lower hydrocarbon radical, X is an oxo group, an alkylenedioxy group or o-phenylenedioxy group containing 2-6 carbon atoms or the grouping H ₁ OR ^, where R. is a hydrogen atom ι a lower alkanoyl or a tetrahydropyranyl group, and a double bond in ^, 5-t 5 »6- or 5» 1O- ^ Position mean, characterized, that one 15ß-Halogentnethyl-17ß-hydroxy steroids of general formula II (II), 030038/0260 R ₁ -P ₀ , R-, X and , L · the above meaning 1 2 3 ./^ \ have and Z is a chlorine, bromine or iodine atom means, treated with a strong, anhydrous base in a polar, aprotic solvent and optionally hydrogenated a 17α-alkynyl group to the alkenyl or alkyl group and / or hydrolyzed 3-ketals or 3-tetrahydropyranyl ethers and / or oxidized or esterified 3-hydroxysteroids. 030038/0260