IMPROVED OMEPRAZOLE PROCESS AND COMPOSITIONS THEREOF

摘要

The present invention describes an improved process for the preparation, isolation, and purification of the anti-ulcer agent omeprazole whereby the sulfide precursor pyrmetazole is reacted subsurfacely with exactly one molar equivalent of meta-chloroperoxybenzoic acid in a chlorinated aliphatic hydrocarbon or aromatic hydrocarbon solvent, such as methylene chloride or toluene; residual organic solvent is removed from the aqueous layer by vacuu m distillation; crude product is obtained by reactive crystallization with an alkyl formate or formic acid solution and seeding; and pure product is isolated by recrystallization in methanol-water containing aqueous NaOH by subsurface addition of aqueous acetic acid to pH 9.0, seeding, filtration, washing, and drying. Omeprazole and compositions of omeprazole containing no chromatographically detectable levels of residual non-alcoholic organic reaction solvent and diminished levels of alcoholic solvent are also describ ed.