New process for the preparation of 6ª--fluoro-steroids

摘要

The invention comprises 5a ,6a -difluoro steroids of the androstane and pregnane series, particularly those of the general formulae:- in formula I, R1 is H(b -OH) or = O, R2 is H or CH3, R3 is = O, H(b -OA) or hydrocarbon (b -OA) in which A is H or Acyl, X is halogen or hydrogen when Y is H(OH) or =O and R2 is CH3, and X is hydrogen when Y is H2, H(OH) or =O; in formula II R1 is H(b -OH) or =O, R2 is H, OH or OAcyl, R3 is H, OH or OAcyl, R4 is H or CH3, Y is H2, H(OH), or =O and X is H or may be halogen when Y is H(OH) or =O; in formula III R1 is H(b -OH) or =O, R2 is H or Acyl, R3 and R4 represent H or an acyl group, or jointly form an isopropylidene group, X and Y are as in formula II, together with a process for their preparation and that of the corresponding D 4-6a /fluoro-3b -hydroxy (or 3-keto) steroids by reacting a 3b -hydroxy-D 5-steroid with anhydrous hydrogen fluoride in the presence of lead tetra-acetate or lead dioxide, preferably in an inert solvent and between -80 DEG and -10 DEG C. to form a 3b -hydroxy-5a ,6a -difluoro steroid, oxidising the 3-hydroxy group to a 3-keto group and then treating the product with an acid or a base to form a D 4-3-keto-6a -fluoro compound. The invention is illustrated by thirty-two detailed examples.