Patent ID: 6603022
Filing Date: 2003-08-05
Classification: C07D

Abstract:
A process for manufacturing Simvastatin of formula II: the process comprising steps of:(a) reacting Lovastatin of formula IIa: â€ƒwith a secondary amine under suitable conditions to form the corresponding amide intermediate of formula IIb: wherein R1 and R2 are each independently an alkyl, heteroalkyl, aryl or heteroaryl moiety, or R1 and R2, taken together, form a heterocyclic moiety having 5-8 atoms; wherein each of the foregoing alkyl and heteroalkyl moieties may be linear or branched, substituted or unsubstituted, cyclic or acyclic or saturated or unsaturated, and each of the foregoing heterocyclic, aryl and heteroaryl moieties may be substituted or unsubstituted; (b) methylating the C-8 butyrate side chain of the amide intermediate (IIb) under suitable conditions to form the corresponding 2,2-dimethylbutyrate intermediate of formula IIc: â€ƒwherein R1 and R2 are as defined above; (c) hydrolyzing the 2,2-dimethylbutyrate intermediate to the corresponding free carboxylic acid; and (d) effecting lactonization of the carboxylic acid intermediate thereby forming the desired Simvastatin of formula II.