PREPARATION OF 17 -PROPADIENYL STEROIDS

摘要

1310612 17α- (3 - Hydroxypropynyl) steroids and derivatives SYNTEX CORP 14 April 1970 [18 April 1969 17 Nov 1969] 41158/72 Divided out of 1310611 Heading C2U Novel steroids of the formulae (wherein R is tetrahydrofuran-2-yloxy, tetrahydropyran - 2 - yloxy, 4 - methoxytetrahydropyran - 4 - yloxy, halo, optionally substituted alkylsulphonyloxy or arylsulphonyloxy or hydroxy; R1 is H or C 1-3 alkyl; R2 is H or acyl or OR2 is etherified hydroxy as defined for R; R3 is O orα-H(#-OR6) in which R6 is H or acyl or OR6 is etherified hydroxy as defined for R; R4 is H or CH 3 ; and R‹ is H, C 1-8 alkyl, cycloalkyl, tetrahydrofuran-2-yl, tetrahydropyran-2- yl, 4 - methoxy - tetrahydropyran - 4 - yl or acyl, with the proviso that, in the estratrienes, when R1 is H, R2 is H or C 1-10 acyl of M.W. below 200, and R5 is H, C 1-8 alkyl, cycloalkyl of 5 or 6 ring members, or C 1-10 carboxylic acyl of M.W. below 200, then R is not OH) and the ketals of the 3-keto steroids are prepared (i) when R is etherified OH, by treating the corresponding 17-oxo steroid with the Grignard reagent prepared from appropriate propargyl ethers and ethyl magnesium bromide; (ii) when R is OH, by hydrolysis of the products of (i), or by reacting the corresponding 17α-ethynyl steroids (in which R2 is preferably an etherifying group) as their Li salts with paraformaldehyde; (iii) when R is halo, by halogenation of the products of (ii) with SOCl 2 , SOBr 2 , PCl 5 , PBr 5 or hydrocarbon sulphonyl fluorides; or (iv) when R is alkyl- or aryl-sulphonyloxy, by esterification of the products of (ii). The products may be subjected to standard etherifications, esterifications, hydrolyses and reductions. All these processes and the preparation of starting materials therefor are described in detail in examples in Specification 1,310,611 from which the present Specification is divided.