PROCESS FOR THE PREPARATION OF DES A-9BETA-STEROIDS

1336894 De-A-9#-steroids F HOFFMANNLA ROCHE & CO AG 21 May 1971 [21 May 1970] 16377/71 Heading C2C The invention comprises certain de-A-9#- steroids of Formula I below, and a process for preparing de-A-9#-steroids in general (which may be optically active or racemic) by hydrogenating the corresponding de-A-#9-steroids in an organic solvent with a palladium catalyst in the presence of hydrogen bromide. In some cases acyloxy groups in the starting materials may be converted simultaneously to hydroxyl groups. Hydroxyl groups in the products may subsequently be esterified. The products may be purified from the 9α-isomers which may be formed in minor amounts in the hydrogenation by fractional crystallization or by refluxing in hexane (Example 6). Preferred products have the formula wherein R1 is C 1-8 alkyl; R2 is H, C 1-8 alkyl, 3- oxobutyl, ketalized 3-oxobutyl, 3-chlorobut-2- enyl, 2-carboxyethyl, 2-alkoxycarbonyl-ethyl, 2-cyanoethyl, or a group of formula wherein R3 and R4 are identical C 1-8 alkyl groups, or one is H and the other is C 1-8 alkyl; and D is a grouping of formula wherein Z is a carbonyl group or a grouping of formula wherein R5 is free/etherified/esterified hydroxyl; R6 is H or C 1-8 alkyl; R7 is H or OH; R8 is H, OH or C 1-8 alkyl; and R9 is free/esterified hydroxyl. Compounds of Formula I claimed per se are those wherein R2 is 3-oxobutyl, ketalized 3- oxobutyl, 3 - chlorobut - 2 - enyl, 2 - carboxyethyl and 2-alkoxycarbonyl-ethyl. Compounds of Formula I may be converted into tetracyclic 9#,10α-steroids as described in Specification 1,336,895 and in Belgian Specifications 697,157 and 742,090 (U.K. equivalents 1,155,511 and 1,298,214). Trans - anti - 6 - (2 - carboxyethyl) - 3amethyl - 3,7 - dioxo - 1,2,3a,4,5,7,8,9,9a, 9bdecahydro - 3H - benz[e]indene (XI) is prepared from 5,5-ethylenedioxy-nonanedinitrile (X) by the sequence: X -# 5-oxo-nonanedinitrile -# 5 - hydroxy - nonanedinitrile -# 8- cyano - 5 - octanolide -# 6 - (3 - cyanopropyl)- 2 - (2 - diethylaminoethyl) - tetrahydropyran - 2- ol -# 3 - (3 - cyanopropyl) - 6a - methyll,2,3,5,6,6a - hexahydro - cyclopenta[f][l]- benzopyran - 7(8H) - one -# 3 - (3 - cyanopropyl)- 6a - methyl - 1,2,3,5,6,6a,7,8 - octahydro - cyclopenta[f][l]benzopyran - 7# - ol -# 6a,9a - trans- 3 - (3 - cyanopropyl) - 6a - methyl - 1,2,3,5,6,6a- 7,8,9,9a - decahydro - cyclopenta[f][l]benzopyran - 7# - ol -# 4 - (6 - cyano - 3 - oxo - hexyl)- 7α - methyl - perhydroindane - 1,5 - dione -# trans - anti - 6 - (2 - cya