Process of synthesis of 5-methoxy-2-[(4-methoxy-3,5-dimethyl-2-pyridyl)methyl] sulfinyl-1 H-benzimidazole

Abstract

An improved process of synthesis of 5-methoxy-2-[(4-methoxy-3,5-dimethyl-2-pyridyl)methyl]sulfinyl- 1 H-benzimidazole (omeprazole) by oxidation of 5-methoxy-2[[(4-methoxy-3,5-dimethyl-2-pyridyl)methyl]thio]benzimidazole with 3-chloroperoxybenzoic acid in ethyl acetate wherein omeprazole is poorly soluble, at a temperature between −10° C. and 5° C. is disclosed. The second step is a purification of the crude product by dissolution and reprecipitation of the final product.

1 . Process for preparing 5-methoxy-2-[(4-methoxy-3,5-dinethyl-2-pyridyl)methyl]sulfinyl-1H-benzimidazole (omeprazole) of the formula  
       
         
           
           
               
               
           
         
       
       characterized in that 5-methoxy-2-[[(4-methoxy-3,5-dimethyl-2-pyridyl)methyl]thio]benzimidazole is reacted with 3-chloroperoxybenzoic acid in ethyl acetate at a temperature between −10° C. and 5° C. and the product formed is purified by dissolution in an aqueous solution of methylamine, by precipitation under addition of hydrochloric acid and isolation of the title compound in a pure form.