Process for the preparation of HMG-CoA reductase inhibitors and intermediate compounds employed therein

Claim 1

A process for the preparation of compounds of the following structural formula (I): ##STR21## wherein R 1 is selected from the group consisting of: (a) ##STR22## wherein Q is ##STR23## R 6 is H or OH; R is hydrogen or methyl, and a and c except when R 6 is OH or b and d represent double bonds or all of a, b, c and d are single bonds; or (b) ##STR24## wherein E is --CH 2 --, --CH 2 CH 2 -- or --CH═CH--; R 2 and R 3 independently are C 1-3 alkyl fluoro, chloro or bromo; and R 4 is phenyl, benzyloxy, substituted phenyl or substituted benzyloxy in which the phenyl group in each case is substituted with one or more substituents selected from C 1-3 alkyl, fluoro, bromo or chloro; which comprises: (A) reacting a compound of the formula (II): ##STR25## wherein R 5 is C 1-5 alkyloxy, benzyloxy or 2-thiopyridinyl; and R 7 is C 1-5 alkyl, benzyl, C 2-5 alkoxyalkyl, C 3-6 alkoxyalkoxyalkyl, tri-C 1 -C 5 -alkylsilyl or tetrahydropyranyl with a compound of the formula (III): R.sup.1 X (III) wherein R 1 is defined above; and X is a metal atom or metal complex selected from Li, MgCl, MgBr, (CuMgCl) 1/2 , (CuMgBr) 1/2 , (CuLi) 1/2 , (CuLi 2 CN) 1/2 or CeCl 2 to afford a compound of the formula (IV): ##STR26## (B) hydrolyzing the compound of the formula (IV) under acidic conditions to afford a compound of the formula (V): ##STR27## (C) stereospecifically reducing the ketone function in a compound of the formula (V) with tri-C 1-5 -alkylborane and alkali metal borohydride at low temperatures to afford a compound of the formula (VI): ##STR28## (D) lactonizing the compound of the formula (VI) by first saponifying the amide followed by acidic treatment to afford the compound of the formula (I).