Procedure and intermediate products for the production of 7-substituted antiestrogens

摘要

A process for preparing an intermediate of formula (II) ** Formula ** wherein X is S; n is 9; R is hydrogen or a hydroxy protecting group, R1 is - (CH2) 3CF2CF3; R2 is hydrogen, (C1-C6) alkyl or hydroxyl, R3 is hydrogen, (C1-C6) alkyl, (C2-C6) alkenyl or (C2-C6) alkynyl; R4 is hydroxy, C1-C10 alkanoyloxy, carboxy-C1-C10 alkanoyloxy or aroyloxy (such as benzoyloxy); R5 is (C1-C6) alkyl; process comprising aromatizing a compound of formula (III) ** Formula ** wherein R1, R2, R3, n, X and R5 are as defined in relation to formula (II) and R4 'is a group R4 or a precursor group thereof, and subsequently if necessary or desired, perform one or more of the following steps: (i) removing any R-protecting groups from hydroxyl groups; (ii) converting a precursor group R4 'to a group R4, or when R4' is a group R4 converting it into such a different group; wherein the compound of formula (III) is prepared by reacting a compound of formula (IV) ** Formula ** wherein R2, R3 and R5 are as defined in relation to formula (II), and R4 'is as defined in relation to formula (III), with a compound of formula (V) ** Formula ** where n, X and R1 are as defined in relation to formula (II) and Z is a metal halide of formula R11-M where M is a metal ion and R11 is a halogen atom.