GB893071A - Improvements in or relating to the preparation of 17-alpha-haloprogesterones and related products - Google Patents

Abstract

The invention comprises steroids of the formula <FORM:0893071/IV (b)/1> (wherein X is chlorine or bromine, R is H, OH or acyloxy and R1 is H,=O (ketonic oxygen) or b -OH and when R1 is not hydrogen, R is not hydrogen) and their preparation (1) when R1 is H or =O, by hydrolysis and oxidation, and partial dehalogenation, in either order, of steroids of the formula <FORM:0893071/IV (b)/2> (wherein R and X have the above values, R1 is H or =O, and AcO is acyloxy) to give steroids of the formula <FORM:0893071/IV (b)/3> and the subsequent reaction of these with an acid; or (2) when R is OH or acyloxy, and R1 is =O or b -OH, by monohalogenating in the 17-position a steroid of the formula <FORM:0893071/IV (b)/4> (wherein R is H or acyl and R1 is =O or b -OH), effecting oxidation in the 3-position and halogenation in the 4-position in one or more stages to give a steroid of the formula <FORM:0893071/IV (b)/5> and then dehydrohalogenating by reaction with semicarbazide or dinitrophenyl-hydrazine and subsequent hydrolysis with an acidic agent; or (3) when R and R1 have the same values as in (2), monohalogenating in the 4-position a steroid of the formula <FORM:0893071/IV (b)/6> (wherein R1 is =O or b -OH and Ac is acyl), protecting the 3-keto group by conversion to the 3-ethyleneketal, effecting halogenation in the 17-position, removing the protecting group, and subsequently dehydrohalogenating as in (2). Specified intermediates in process (1) have the formula <FORM:0893071/IV (b)/7> (wherein R is acyl, R1 is =O, R2 is H or acyl, and X is chlorine or bromine). Detailed examples are given, and reference is also made to the use of 3-acylated starting materials in method (2), in which the free 3-hydroxy group must be liberated prior to oxidation, for instance, by total hydrolysis of all the ester groups and subsequent partial esterification in position 21. Trihalo-steroids of the second general formula above are prepared either by direct halogenation of suitable D 5-3-acyloxy-11-R1-21-R-pregnen-20-ones or by converting them to a mixture of the corresponding 17-en-20-ol acylates and halogenating this mixture. 17a - Chloro - 3a : 21 - diacetoxy - pregnane - 11 : 20-dione is prepared by chlorinating 3a -acetoxy-pregnane-11 : 20-dione to give the 17 : 21-dichloride, treating this with sodium iodide to give the corresponding 21-iodo-17-chloride and reacting this with potassium acetate.