process for the production of 11ª amp; permil; hydroxy 19 nor testosterone

摘要

The invention comprises a des-A-estrane derivative of the general formula FORM:1016244/C2/1 wherein R9 is either oxygen =O or alkylene dioxy -O(CH2)nO-, wherein n is 2-4; and either R7 is oxygen =O or hydroxy (H1OH) and R8 is H, or R7 and R8 together form in the case when R9 is oxygen, either a 10,11-hemiacetal grouping -CH(OH)O- or a 10,11-lactone grouping -CO.O-, in which latter case there may also be a 10a -(b -acetylethyl) group -(CH2)2CO.CH3; and R1 is an acyl group derived from an organic carboxylic acid containing 1-10 carbon atoms, or in the case when R7 is a hydroxy group (H1OH) or together with R8 is a 10,11-lactone, may be hydrogen, and processes for the preparation thereof by reacting 17b - acyloxy - 5 - alkylenedioxy - 9a ,11a - epoxy-des A-estran with formic acid to obtain a 17b - acyloxy - des - A - estra - 5,11 - dione, ketalizing the latter to obtain 17b -acyloxy-5-alkylenedioxy - des - A - estran - 11 - one, treating the latter with a mixed anhydride to obtain a 17b - substituted - 5 - alkylenedioxy - 11b - hydroxy - des - A - estrane, treating the latter with an acid to obtain a 17b -substituted-11b -hydroxy - des - A - estran - 5 - one, reacting the latter with an alkyl carbonate to form the 10,11-lactone of a 17b -substituted 10b -carboxy-11b -hydroxy - des A - estran - 5 - one and reacting the latter with methyl vinyl ketone to obtain the 10,11-lactone of a 17b -substituted 10b -carboxy - 11b - hydroxy - 4,5 - sec. - estra - 3,5 - dione. Alternatively the 10,11-lactone of a 17b - acyloxy - 10b - carboxy - 11b - hydroxy - des-A-estrane-5-one is obtained by reacting a 17b - acyloxy - 11b - hydroxy - des A - estran - 5-one with an alkyl formate in the presence of an alkali metal alcoholate or hydride to form the 10,11-hemiacetal of a 17b -acyloxy-10b -formyl-11b -hydroxy - des - A - estran - 5 - one, which is reacted with an oxidizing agent to form the 10,11-lactone.