Patent GB-1148618-A (GB)
Title: (optionally 17-alkylated) 17-oxygenated 7-methyl-5ª‡-androst/estr-2-enes
IPC: C07J75/00
Filed: 1967-09-21
Abstract: 1,148,618. #<SP>2</SP> - 3 - Unsubstituted - 7 - methyl steroids. G. D. SEARLE & CO. 21 Sept., 1967 [23 Sept., 1966 (2)], No. 43048/67. Heading C2U. Novel steroids of the formula (wherein R is H or CH 3 ; and X is CO or C(α- R<SP>11</SP>)(#-OR<SP>1</SP>), R<SP>11</SP> being H or C 1-7  alkyl and R<SP>1</SP> being H or C 1-7  alkanoyl) are prepared (1) by pyrolysis of corresponding ring A saturated 3#-chloro or 3#-acyloxy steroids or, in the case of the 3#-acyloxy-17-ols, of the corresponding 17-ethers, in which the acyl group is such as acetyl or p-toluenesulphonyl, methanesulphonyl, p-bromobenzenesulphonyl or benzenesulphonyl in the presence respectively of a base or of an amine such as collidine, and when required, removal of the 17-ether group; or (2) by treatment of the 3#-sulphonyloxy starting materials of (1) with sodium or potassium acetate and acetic acid, with KOH/CH 3 OH or with Li 2 CO 3  in dimethylacetamide, or by their decomposition on alumina; or (3) by treatment of corresponding ring A saturated 2,3-(trans)- bromohydrins with chromous chloride in an inert solvent or with zinc in acetic acid, or (4) by LiAlH 4  reduction of corresponding ring A saturated 3-tosyl-hydrazones which may contain a 2α-bromo substituent. In the products 17-ols may be oxidized to 17-ones, these may be reduced to 17-ols or reacted with alkyl metal compounds to give 17α-alkyl-17#-ols, and 17-ols may be acylated. 3a - Bromo - 2# - hydroxy - 7 - methyl - 5α- androstan-17-one is prepared by the action of N-bromosuccinimide and perchloric acid on 7- methyl-5α-androst-2-en-17#-ol and is converted to 7-methyl-5α-androst-2-en-17-one by refluxing with zinc and acetic acid. This process may in general be used for the purification of, for example, 7,17α-dimethyl-5a-androst-2-en-17# -ol via the corresponding 3α-bromo-2#-hydroxy compound, viz. 3α-bromo-7,17α-dimethyl-5α-androstane-2#,17#-diol. 3# - Hydroxy - 7 - methylandrostan - 17 - one 3-p-toluenesulphonate is prepared by contacting 7-methylandrost-4-ene-3,17-one with acetone cyanhydrin in the presence of triethylamine catalyst to give 17-cyano-17-hydroxy-7-methylandrost-4-en-3-one, converting this to the 17- acetate, reducing this to the 3#-ol, reacting this with aqueous KOH in methanol to give 3# hydroxy - 7 - methylandrost - 4 - en - 17 - one, and reducing the double bond and acylating. This is a general route to the 17-keto compounds. In general, 3#-acyloxy starting materials are prepared from precursors of the formula (wherein X<SP>1</SP> is CO, CH(#-OH) C alkyl(#-OH) or ethers of the last two) by concurrent or successive reduction of the 3-keto and #<SP>4</SP> moieties. Examples of these processes describe (1) the reduction of 17#-hydroxy-7-methyl-androst-4-en- 3-one 17-tetrahydropyranyl ether (prepared from the free 17-ol) with Li in liquid NH 3  to give 7- methyl - 5α - androstane - 3#,17# - diol 17 - tetrahydropyranyl ether; (2) the reduction of 17#- hydroxy - 7,17α - dimethyl - androst - 4 - en - 3- one with a metallic hydride to give 7,17α-dimethylandrost - 4 - ene - 3#,17# - diol and catalytic hydrogenation of this to give 7,17α- dimethyl-5α-androstane-3#, 17#-diol; and (3) the processes of (2) reversed in order. Acylation then gives the required starting materials.