Patent ID: 6573392
Filing Date: 2003-06-03
Classification: C07D

Abstract:
A process of manufacturing Simvastatin of formula IIa: the process comprising steps of:step 1â€”converting Lovastatin of formula Ia: â€ƒinto a Lovastatin amide of formula III or V: â€ƒwherein R1 and R2 are independently alkyl and n is 1 or 2; by treating Lovastatin (Ia) with a secondary amine in an organic solvent; step 2â€”reacting the lovastatin amide of formula III or V with a metal amide base in tetrahydrofuran (THF) followed by treatment with an alkyl halide and cooling the said mixture at a temperature ranging between âˆ’45Â° C. to âˆ’20Â° C. until a C-methylated intermediate compound of formula IV or VI is formed: step 3â€”subjecting the intermediate compound of formula IV or VI to hydrolysis to obtain the corresponding free acid; and step 4â€”converting the free acid to the corresponding ammonium salt and cyclizing the ammonium salt to obtain simvastatin (IIa).