NO154276B - DEVICE FOR FOAMS OF FLOATING SUBSTANCES. - Google Patents

Abstract

Device for skimming substances floating on water, in particular oil, with an inlet inclined surface (1) inclined towards the water surface, the front end (10) of which is below and the rear end (9) of which lies above the waterline (7) including the oil layer (7a). At least one catchment opening (17) is arranged in the inlet inclined surface (1) above the waterline, including the oil layer, which opening is connected to a catchment space (2). The on-sloping slat encloses an acute angle with the lower edge (8) of the catchment space and extends from this and upwards. The feed-on inclined surface together with the catch pipe (2) forms part of a floating body. The front edge (10) of the inlet inclined surface (1) forms the lowest area below the waterline (7) of the device section arranged after the inlet inclined surface (1), and on the leading edge a flow is arranged over the entire width of the inlet inclined surface. profile body (10).

Description

Process for the production of therapeutically active steroid ketones with 17-haloalkynyl groups.

This invention relates to methods for the production of steroid ketones with 17-haloalkynyl groups, and certain of their derivatives.

In Norwegian patent no. 122 643, a method for the production of a 13-polycarbonalkyl-gon-4- or 5(10)-en-3-one is specified; these compounds have useful pharmaceutical activity or are intermediates for the preparation of other compounds with such activity. It has now been found that certain members of that class as well as other closely related compounds, all of which are novel, exhibit surprisingly better pharmaceutical activity than the rest of the class.

The method according to the invention is one for the production of a new steroid ketone with the structure:

where each group R is hydrogen or an alkyl group containing up to 5 carbon atoms, R<1> is an n-alkyl group with 2 to 4 carbon atoms, R 2 is a haloalk-l-ynyl group containing up to 5 1 3 carbon atoms and in trans configuration in relative to R , OR is a hydroxy group, an etherified hydroxy group with up to 5 carbon atoms, preferably a tetrahydropyranyloxy group, or an acyloxy group with up to 19 carbon atoms, Q is a methylene or ethylene group, the substituents on the tertiary carbon atoms in ring c are in trans-anti -trans configuration, and ring A contains a double bond in the 4(5) or 5(10) position and the method is characterized by hydrolyzing a steroid ketone derivative with the general formula

12 3

where R, R, R, R, Q and the configuration of ring C are as above, and X means an acid-hydrolysable, protected 3-oxo group, containing an organic group attached to ring A through oxygen, sulfur or nitrogen in combination with a double bond attached to the 5-position and with or without another double bond attached to the 3-position, under mild conditions to a gon-5(10)-en-3-one or under strong conditions to a gon-4-en- 3-one, and optionally one isomerizes a gon-5(10)-en-3-ori product to a gon-4-en-3-one product, or optionally etherifies or acylates a product where OR 3 is hydroxy , and eventually

a 3-enol acylate obtained by the acylation is selectively hydrolysed.

An alkyl group can in this context be a linear one

or branched group. When a group R is an alkyl group, it can e.g. be a methyl or ethyl group.

R"*" can e.g. be an ethyl, n-propyl or n-butyl group. R is a haloalkynyl group with its acetylene bond at the carbon atom closest to the steroidal ring D. Examples of haloalkynyl groups are chloroethynyl (ClC=C-), bromethynyl, fluoroethynyl and trifluoromethylethynyl groups. R 30 can be hydroxy, an etherified hydroxy group with up to 5 carbon atoms, e.g. a 2-tetrahydro-pyranyl group, or an acyloxy group of up to 19 carbon atoms, e.g. an acetoxy or n-heptanoyloxy group. Especially valuable are those compounds in which each group R is hydrogen, or only one group R in the molecule is an alkyl group and this is a methyl group; those in which B?~ is an ethyl group; those in which R 2 is a chloroethynyl group; and those in which R 1 is hydrogen. In the compounds with structure (II), the group X, which is in the 3-position in the steroid molecule, contains an organic radical bound to ring A with oxygen, sulfur or nitrogen. The organic radical can be bound to the carbon atom in the 3-position with two such heteroatoms. ;Examples of suitable X groups are alkoxy groups (e.g. ;a methoxy, ethoxy, methoxymethoxy or dihydroxypropyloxy group), alkylthio groups (e.g. an ethylthio or benzylthio group), dialkylamino groups (e.g. a N-pyrrolidyl group), alkylenedioxy groups (eg an ethylenedioxy group) or alkylenedithio or alkylenedioxy groups. ;The unsaturation present in ring A or ring B which is ;attached to the group X can consist of a single ethylene bond ending in the 5-position (so it can be in the 4,5-, 5,6- or 5,10- the position). The unsaturation can also be in the form of two ethylene bonds, one of which ends at the 3-position (so it can be in the 2,3- or 3,4-position), and the other at the 5-position, and such ethylene bonds can be conjugated or unconjugated. The compounds with one ethylene bond are those in which two heteroatoms are bound to the carbon atom in the 3-position, and examples of these are 3-ketals, 3-mercaptols and 3-hemithioketals, all of which represent derivatives of a 3-ketone. The compounds with two ethylene bonds are those which only have a heteroatom attached to the carbon atom in the 3-position, and examples of these are enoleters, enolthioethers and tertiary amino compounds, which represent derivatives of the enol form of a 3-ketone. ;Suitable starting materials for the hydrolysis process are mixtures of 3-Alkoxy-3,4- and -3,5(10)-dienes (enoleters from 4,5-ethylene 3-ketones), 3-Alkoxy-2,5(1/) -dienes (enol ethers of 5,10-ethylene 3-ketones), 3-acyloxy-3,5-dienes (enol esters of 4,5-ethylene ketones), mixtures of 3,5-alkylene-dioxy-5- and ;-5 (10)-enes (alkylene ketals from 4,5-ethylene-3-ketones), 3,3-alkylene-dioxy-5(10)-enes (alkylene ketals from 5,10-ethylene 3-ketones); and 3-tertiary alkylamino-3,5(6)-dienes (the tertiary amines from 4,5-ethylenic 3-ketones). Particularly important are those derivatives in which x is an alkoxy group (e.g. methoxy) and ring A has ethylene bonds in the 2(Sj- ;and 5(10)-positions, those in which x is an ethylenedioxy group and the ring A and the ring B has an ethylene bond in either the 5(6) or 5(10) position, and those in which X is an alkoxy group and the rings A and B have ethylene bonds in the 3(4) and 5(6) or 5(10) )-positions. ;Starting material with structure (II) where R 3 is hydrogen ;can be prepared by alkylating the corresponding 17-ketone in the 17-position, with the introduction of a haloalk-l-ynyl group R 2. This method is described in French Patent No. 1,566,154. Hydrolysis of a steroid ketone derivative of structure (II) to the steroid ketone of structure (I) can be carried out by contacting the starting material with an acid and water at a suitable temperature. compound that is hydrolysed is preferably a 3-Alkoxy-2,5(10)-diene When the starting material contains an ethylene bond in the 5,10 position, 6Y-unsubstituted ketones (gon-5( 10)-en-3-ones) according to the invention are prepared under mild hydrolysis conditions, such as with aqueous, alcoholic oxalic acid at 30°C; and below; under more strongly acid conditions, such as e.g. with 6N aqueous hydrochloric acid at room temperature, isomerization to the α-B-unsaturated ketones (gon-4-en-3-ones) is facilitated, and the recovered product is the conjugate. When the starting material does not contain an ethylene bond in the 5(10) position, hydrolysis takes place to form the ketone with conjugated unsaturation. In some cases, e.g. when X is an acyloxy group, the hydrolysis reaction can be carried out using a base, e.g. sodium hydroxide in aqueous methanol. In many cases hydrolysis with water is unnecessary and all that is required is a hydroxylic medium, e.g. an alcohol or a carboxylic acid. Steroid ketones produced by the method according to the invention, which have an ethylene bond in the 4(5) position, can also be produced by isomerization of the corresponding compounds with an ethylene bond in the 5(10) position. This isomerization can be carried out under basic conditions, such as e.g. with aqueous, alcoholic sodium or potassium hydroxide at room temperature, or with sodium alkoxide in an alcohol at 60°C. Strong acid conditions, such as heating in methanol with concentrated hydrochloric acid, can also be used. The isomerization process occurs so that the hydrogen atom in the 10-position appears anti to the hydrogen atom in the 9-position. ;A compound of the structure (I) where OR"* is a hydroxy group can be preferred in the 17-position to form a compound where OR 3 is a preferred hydroxy group, e.g. by reaction with 2,3-dihydropyran to form a tetrahydropyranethers A compound of structure (I) where OR 3 is hydroxy, the double bond in the 4(5) position can be acylated to form a 3,17-diacylgona-3,5-diene, followed by selective hydrolysis of the 3-enol acylate group to form a gon-4-en-3-one of structure (I), where OR is an acyloxy group.

In the above structures (I) and (II) the 13S and 13a compounds are not completely separated, as the 13S and 13a forms in the product after a total synthesis that has not included a suitable separation step will be present in equimolecular amounts or in racemate form. Preferably, the starting material in the method according to the invention is a separated 13B enantiomer. The invention includes in particular the preparation of enantiomers with the 13B-alkyl group,

in the presence or absence of its 13a-alkyl enantiomers, so that it comprises the preparation of the separated 13B-ethyl compounds and the 13B-forms in admixture with the corresponding 13a-forms, especially racemic forms.

The products produced by the method according to the invention are useful either as pharmaceutical preparations with progestational activity, pituitary gonadotropic inhibitory activity,

or other valuable steroidal hormone properties, or as intermediates for such drugs. Compounds with structure (I) can e.g. is reduced with a borohydride to give the corresponding 3-ol which can optionally be acylated to give the 3-acyloxy compound. This method is described in French patent no. 1 566 154.

It has been found that the properties of the drug preparations are generally superior to or different from the properties of the corresponding compounds with a 13-methyl group. However, the difference in properties between the products produced by the method according to the invention and the corresponding 13-methyl compounds is not only a difference in degree, but also a qualitative difference.

In particular, it has been observed that homologation with an additional carbon atom in the 18-position (so that one obtains a 13-ethyl group) generally results in the valuable properties of the corresponding 13-methyl compounds being retained and increased. Products prepared by the method according to the invention with n-propyl or n-butyl in the 13-position generally show less activity, but are still valuable, because they show special activities which are different from those shown by the corresponding 13-methyl compounds.

PROGESTATIONAL ACTIVITY

Measurement of progestational activity by the Clauberg method according to Elton and Edgren, Endocrinoloqy, 1958, 6_3, 464, has given the following results:

The (+)-13B-methyl compound listed for comparison is one of the most active progestational agents known to date. The activities of the 13B-ethyl compounds are remarkable, especially as the active (+)-enantiomers will have correspondingly higher activity.

PITUITARY GONADOTROPIC INHIBITORY ACTIVITY

In an experiment to measure pituitary blockade activity, the ovary is removed on one side of adult female rats, and these are treated daily for 14 days with the test compound. At autopsy on the 15th day, the remaining ovary (the left one) is removed and weighed. Hemicastration partially frees the hypothalamic-pituitary system

from the ovarian secretion, which is measured on the basis of a compensatory

overgrowth (hypertrophy) of the remaining ovary. Active compounds prevent this overgrowth, probably by blocking gonadotrophin secretion. The following results were obtained in this experiment:

The (+)-13B-methyl compound is used as a standard for comparison and the stated results show a remarkably increased activity for the compounds according to the invention, especially considering that they are racemates.

ESTROGEN ANTAGONISTIC ACTIVITY

Estrogen-antagonistic activity as measured by the mouse vaginal smear test according to Edgren, Proe. Soc. Exp. Biol. Med., 1960, 105, 252 gave the following results:

Steroid ketones according to the invention which have a 5,10-ethylene bond are also valuable as chemical intermediates for the production of the corresponding 4,9(10)-dien-3-ones, as described in Swedish patent no. 330 381.

The invention is illustrated by the following examples, where the temperature values are in °C. Infrared absorption data (IR) refer to maximum values given in cm~^, and ultraviolet absorption data (UV) refer to maximum values given in nya with the number in parentheses indicating molecular extinction coefficients at these wavelengths.

EXAMPLE 1

PREPARATION OF STARTING MATERIALS FOR EXAMPLES 4 AND 7.

(±)-13B-ethyl-3-methoxygona-2,5(10)-dien-17-one (8 g) was added with stirring to lithium chloroacetylide (prepared from lithium methyl, 5.53 g, and cis-1,2 -dichloroethylene, 16.9 g) in ether (100 ml) under nitrogen. The mixture was stirred for 48 hours at room temperature, poured into water and the product was isolated using ether. The resulting solid was triturated with hot methanol, cooled and the crystalline solid was filtered off as crude (±)-17a-chloroethynyl-13B-ethyl-3-methoxygona-2,5(10)-dien-17B-ol (4.5 ml); IR: 3390, 2200, 1695, 1670.

EXAMPLE 2

PREPARATION OF STARTING MATERIALS FOR EXAMPLES 5 AND 8.

(±)-3-methoxy-13B-n-propylgona-2,5(10)-dien-17-one (8 g)

in ether (250 mL) was added with stirring under nitrogen to lithium chloroacetylide (from lithium methyl, 5.53 g), and cis-dichloroethylene, 16.9 g) in ether (300 mL). The mixture was stirred for 20 hours at room temperature, and the solution cooled using a -70°C bath, saturated aqueous ammonium chloride (50 mL) was then added dropwise, followed by water (200 mL), and the mixture was allowed to stand to achieve room temperature. The ether layer was separated, washed with water, dried and evaporated and a residue was obtained which was recrystallized from methanol to give (±)-17a-chloroethynyl-3-methoxy-13B-n-propylgona-2,5(10)- dien-17B-ol (2.5 g), m.p. 110-116°C; IR: 2200, 1685, 1660.

••v'"- EXAMPLE 3

p,. v.. PREPARATION OF STARTING MATERIALS FOR EXAMPLES 6 AND 9.

To lithium methyl (94.6 g) in ether (300 mL) was added cis-cbrethylene (11 g) over one hour, followed by (±)-13B-ethyl--D-homp-3.-metpcoxygona-2 , 5(10)-dien-17a-one (12 g) suspended in ether (200 ml), at room temperature with stirring. The mixture was then cooled in an ice bath and saturated aqueous ammonium chloride (250 mL) was added dropwise. The separated ether layer was washed, dried and evaporated; Trituration of the crystalline residue with boiling methanol (100 mL) gave (<+>)-17aa-chloroethynyl-13B-ethyl-D-homo-3-methoxygona-2,5(10)-dien-17aB-ol (13 g ), sm.p. 120-126°C (dec.), IR: 3340, 2200, 1695, 1670.

EXAMPLE 4

(±)-17α-chloroethynyl-13B-ethyl-3-methoxygona-2,5(10)-dien-17B-ol (2.5 g) was added to a mixture of methanol (100 mL), dioxane (200 mL ) and oxalic acid (the dihydrate, 2 g) and the mixture was stirred for 2 hours. Water was then added and the product was isolated using ether. Successive crystallization

ring from a mixture of ethyl acetate and hexane, and from acetonitrile gave (+)-17α-chloroethynyl-13B-ethylgon-5(10)-ene-17B-ol-3-one (1.9 g),

sm.p. 110-114°C; IR: 3390, 2200, 1710. Recrystallization of a sample for analysis from a mixture of ether and hexane increased the melting point to 115-120°C).

(Found: 73.2% C, 8.0% H, 9.7% Cl

<C>21<H>27°2Cl requires: 72.8% c' 7.85%H,10.2% Cl).

EXAMPLE 5

Oxalic acid (dihydrate, 1.2 g) in water (10 mL) was added with stirring to (±)-17α-chloroethynyl-3-methoxy-13B-n-propylgona-2,5(10)-diene-17B-oI (1.0 g) in isopropyl alcohol (150 mL) under nitrogen. The mixture was stirred for 2 hours, poured into water and the precipitate filtered off and dried as crude (±)-17a-chloroethynyl-13B-n-propylgon-5(10)-en-17B-ol-3-one, sm .p. 145-150°C. This was purified by dissolving a portion in benzene followed by chromatography on silica gel; washing with a mixture of benzene and ether followed by removal of solvent and recrystallization from a mixture of ether and hexane gave the crude compound (0.35 g), m.p. 174-176°C;

IR: 3470, 2210, 1715.

(Found: 73.5% C, 8.4% H

<C>22<H>29°2Cl requires: 73.2% C, 8.1% H).

EXAMPLE 6

(±)-17aa-chloroethynyl-13B-ethyl-D-homogona-2,5(10)-dien-17aa-ol (2.5 g) in tetrahydrofuran (20 mL) was added to methanol

(80 ml) which contained water (10 ml) and oxalic acid monohydrate (1.75 g).

A solid material was precipitated almost instantly; additional tetrahydrofuran (20 mL) was added and the mixture stirred under nitrogen for 45 minutes. The resulting clear solution was completely brined and the product isolated with ether and recrystallized from a mixture of ethyl acetate and hexane to give (±)-17aa-chloro-ethynyl-138-ethyl-D-homogon-5(10)-ene -17α6-ol-3-one (1.4 g), m.p. 150 - 154°C; IR: 3480, 2210, 1715.

EXAMPLE 7

Crude (±)-17α-chloroethynyl-13B-ethyl-3-methoxygona-2,5(10)-dien-178-ol (3 g, obtained as described in Example 1) was stirred in methanol (36 mL) containing 11 N hydrochloric acid (2.4 ml) and water

(1.6 mL) for 30 minutes. Water was then added and the product isolated with ether and purified by taking it up in benzene and chromatography of the resulting solution on neutral alumina; washing with ether and recrystallization of the isolated product from a mixture of ethyl acetate and hexane gave (±)-17α-chloroethynyl-13B-ethylgon-4-ene-17B-ol-3-one (1 g), m.p. 183-184°C (splitting), after previous melting with resolidification at 152-154°C. Samples obtained by recrystallization of the chromatographed material from a mixture of methanol and water (3 parts to 1 by volume) had m.p. 187-190°C (dec.); UV: 240 (16,800); IR: 3280, 2200, 1655;

(Found: 72.7% C, 7.8% H, 10.2% Cl.

C21<H>27°2C1 required: 12' 7°/ o c 7.8% H, 10.2% Cl).

EXAMPLE 8

Crude (±)-17c£-chloroethynyl-13B-n-propyl-3-methoxy-gona-2,5(10)-dien-178-ol (5.5 g, obtained as described in Example 2) was stirred in methanol (90 mL) containing isopropyl alcohol (10 mL) and water

(4 mL) with 11 N hydrochloric acid (6 mL) for 30 min under nitrogen. The mixture was then diluted with water, the product isolated by means of ether and purified by taking it up in benzene and chromatographing the resulting solution on activated calcareous earth. Elution with benzene containing a small amount of ether and isolation of the product followed by recrystallization from a mixture of ethyl acetate and hexane gave (±)-17α-chloroethynyl-13B-n-propylgon-4-ene-17B-ol-3-one (1.1 g), mp 179-81°C; UV: 240 (16,900); IR: 3460, 2200, 1670.

(Found: 73.5% C, 8.2% H, 9.9% Cl.

<C>22<H>29°2C1 requires: 73.2% C, 8.1% H, 9.8% Cl).

EXAMPLE 9

(±)-17aa-chloroethynyl-13B-ethyl-D-homo-3-methoxygona-2,5(10)-dien-17a«-ol (13 g) was suspended in methanol (180 ml) containing tetrahydrofuran (15 ml), dioxane (15 ml), water (8 ml) and concentrated hydrochloric acid (12 ml) and the mixture was stirred under nitrogen for 45 minutes. The resulting clear solution was poured into saline

ning and the product isolated by means of ether; recrystallization from a mixture of ethyl acetate and hexane gave (±)-17aa-chloroethynyl-13B-ethyl-D-homogon-4-ene-17a8-ol-3-one (7.4 g), m.p. 204-6°C;

UV: 240 (16,800); IR: 3450, 2215, 1670.

(Found: 73.5% C, 8.1% H, 9.6% Cl.

<C>22<H>29°2Cl requires: 73.2% C, 8.1% H, 9.8% Cl).

EXAMPLE 10

(±)-17a-chloroethynyl-13B-ethylgon-4-ene-17B-ol-3-one (0.5 g)

was added to 2,3-dihydropyran (5 ml) containing benzene (0.8 ml) and toluene-p-sulfonic acid monohydrate (0.014 g), and the mixture was heated to the boiling point and held at this temperature until dissolution was complete. The solution was then cooled to room temperature and held for 16 hours at this temperature, after which it was diluted with ether and washed with saturated aqueous sodium bicarbonate, then with water and then with brine. Evaporation of the dried solution and crystallization of the residue from hexane gave (±)-17α-chloroethynyl-13B-ethyl-17B-(2'-tetrahydropyranyloxy)gon-4-en-3-one (0.36 g), m.p. p. 125-31°C.

(Found: 72.4% C, 8.1% H, 8.2% Cl.

C26<H>35<0>3<C>1 requires: 72.45% C, 8.2% H, 8.2% Cl).

EXAMPLE 11

PREPARATION OF STARTING MATERIAL FOR EXAMPLE 12

(±)-17α-chloroethynyl-13B-ethylgon-4-en-176-ol-3-one (3.0 g), acetic anhydride (48 ml), acetyl chloride (24 ml) and pyridine (2.4 ml) were heated together under reflux for two hours. The remaining acylating agent and solvent were evaporated under reduced pressure and the residue partitioned between water and a mixture of benzene and ether; the organic phase was washed, dried and evaporated to give crude crystalline (±)-17a-chloroethynyl-3,17B-diacetoxy-138-ethylgona-3,5-diene. A sample after rubbing with cold ether, filtering and washing with hexane, had m.p. 177-80°C;

IR: 2220, 1755, 1740, 1670; UV: 236 (18,800).

EXAMPLE 12

To (±)-chloroethynyl-3,17B-diacetoxy^13B-ethyl-gona-3,5-

The diene (ca. 2.5 g) dissolved in methanol (70 ml) and tetrahydrofuran (70 ml) under nitrogen and cooled to 0°C was added a 2%

solution methanolic potassium hydroxide (200 ml) and the mixture became

stirred at 0°C for one hour. The solution was then poured into brine, the resulting suspension acidified with 10% aqueous hydrochloric acid and the product isolated with ether, taken up in benzene containing a small amount of light petrol, and the solution filtered through neutral alumina. Evaporation of the solvent and recrystallization from a mixture of ether and hexane gave (±)-17B-acetoxy-17a-chloroethynyl-13S-ethylgon-4-en-3-one (1.27 g), m.p. 185-7°C; IR: 2215, 1740, 1670; UV: 240 (16,900).

(Found: 71.0% C, 7.7% H,

C23H29°3Cl requires: 71'°% C' 7'5% H)•

EXAMPLE 13

PREPARATION OF STARTING MATERIAL FOR EXAMPLE 14

A mixture of (±)-17α-chloroethynyl-13B-ethylgon-4-ene-17B-ol-3-one (3.0 g), n-heptanoic anhydride (50 mL), pyridine (2.4 mL)

and n-heptanoyl chloride (25 mL) was heated at 100°C for 3 1/2 hours and cooled; solid pyridinium salt was filtered off and the remaining acylating agent and pyridine were distilled off at 0.5

mm Hg, so that (±)-17α-chloroethynyl-3,17B-diheptanoyloxy-13B-ethylgona-3,5-diene (3.7 g) was obtained as a residue, a small amount of this was crystallized from methanol as a waxy solid material, m.p. 56-65°C; IR: 2880, 2220, 1735.

EXAMPLE 14

To (±)-17α-chloroethynyl-3,17B-diheptanoyloxy-13B-ethyl-gona-3,5-diene (3.5 g) dissolved in methanol (360 ml) under nitrogen and cooled to 0°C was added a 2% solution of methanolic potassium hydroxide (120 ml) and the mixture was stirred at 0°C for two hours. The resulting solution was poured into saturated saline, and the product isolated by means of ether as a gum, which was taken up in benzene, containing a small amount of ether, and filtered through neutral alumina, and (±)-17a-chloroethynyl-138 -ethyl-17B-heptanoyl-oxygen-4-en-3-one was isolated as a non-crystallizable gum (3.7 g).

EXAMPLE 15

13B-ethyl-6-methyl-3-methoxygona-2,5(10)-dien-17-one (2 g) was added with stirring to lithium chloroacetylide (prepared from lithium methyl, 1.4 g and cis-1,2- dichloroethylene, 4.2 g) in ether (25 mL) under nitrogen. The mixture was stirred for 4 hours, cooled in a

ice bath and decomposed by addition of water. The organic layer was separated, washed, dried and evaporated to give a residue consisting of 13B-ethyl-6-methyl-3-methoxy-176-hydroxy-17a-chloroethynyl-gona-2,5(10)-diene. The residue was stirred with concentrated hydrochloric acid (2.4 mL) in water (1.6 mL) and methanol (36 mL) for 2 hours. Water was added and the product was extracted into ether. The ether solution was washed, dried and evaporated and the residue crystallized from ether to give 13B-ethyl-6-methyl-17B-hydroxy-17a-chloro-ethynylgon-4-en-3-one (0.6 g) , sm.p. 172-175°. IR 3.0, 4.53, 6.01, 6.17, 930^.

Analysis:

Calculated for C22<H>2<g>O2Cl: C: 73.21%; H: 8.09%.

Found: C: 73.50%; H: 8.33%.

Claims (3)

1. Process for the production of therapeutically active substances steroid ketones with 17-halogenalkynyl groups and of the general formula where each group R is hydrogen or an alkyl group containing up to 5 carbon atoms, R"*" is an n-alkyl group with 2 to 4 carbon atoms, R 2 is a haloalk-l-ynyl group containing up to 5 carbon atoms and in trans configuration with respect to R 1 , OR 3 is a hydroxy group, an etherified hydroxy group of up to 5 carbon atoms, preferably a tetrahydropyranyloxy group, or an acyloxy group of up to 19 carbon atoms, Q is a methylene or ethylene group, the substituents on the tertiary carbon atoms in ring C are in trans-anti-trans configuration, and ring A contains a double bond in the 4(5) or 5(10) position, characterized by hydrolyzing a steroid ketone derivative with the general formula 12 3 where R, R , R , R , Q and the configuration of the ring C are as above, and X means an acid-hydrolyzable, protected 3-oxo group, containing an organic group attached to ring A through oxygen, sulfur or nitrogen in combination with a double bond attached to the 5-position, and with or without another double bond attached to the 3-position, under favorable conditions to a gon-5(10) -en-3-one or under strong conditions to a gon-4-en-3-one, and optionally a gon-5(10)-en-3-one product is isomerized to a gon-4-en-3- on product, or optionally one etherifies or acylates a product where OR"* is hydroxy, and optionally one selectively hydrolyzes a 3-enol<«->acylate obtained by the acylation. 2. Procedure as stated in claim 1, characterized by the fact that a 3-alkoxy-2,5(10)-diene is used as starting material. 3. Method as specified in one of claims 1 and 2, characterized by using a starting material 1 2 where each R is hydrogen, R is an ethyl group, R is a chloroethynyl group, R<3> is hydrogen, and Q is a methylene or ethylene group.