Process for α-C-alkylation of the 8-acyl group on mevinolin and analogs thereof

Claim 1

A process for the preparation of a compound of structural formula (V): ##STR5## wherein: R 1 is C 1-5 alkyl; R' 2 is selected from the group consisting of H, CH 3 , OSi(Me) 2 t-C 4 H 9 or CH 2 OSi(Me) 2 t-C 4 H 9 ; R 3 is H or C 1-3 alkyl; R 4 is C 3-5 alkyl; R 5 is C 1-3 alyl; and R' 8 is selected from the group consisting of H or OSi(Me) 2 tC 4 H 9 or CH 2 Si(Me) 2 tC 4 H 9 ; provided that at least one of R' 2 or R' 8 is H; a, b and c each represent single bonds or one of a, b and c represents a double bond or both a and c represent double bonds; which comprises: (A) treatment under a inert atmosphere of a compound of structural formula (III): ##STR6## wherein R 2 is selected from the group consisting of H, CH 3 , --OH, or --CH 2 OH; R 8 is selected from the group consisting of H or CH 2 OH; provided that at least one of R 2 or R 8 is H; with an alkyl amine R 4 NH 2 , followed by hydroxyl protection with tert-butyldimethylsilyl chloride and imidazole; then (B) treatment with an alkali metal amide of formula M + N - R 6 R 7 ; wherein M + is a cation derived from sodium potassium or lithium, and R 6 and R 7 are independently C 1-3 alkyl, or R 6 and R 7 joined together with the nitrogen to which they are attached form a 5 or 6 membered heterocyclic ring; followed by contact with R 5 X, wherein X is chloro, bromo or iodo.