Process for the preparation of 2-{4-(3-methoxypropoxy)-3-methylpyridin-2-yl}methylsulfinyl-1H-benzimidazole substantially free of sulfone impurity

摘要

A process for the preparation of rabeprazole substantially free of sulfone impurity is disclosed. The method comprises reacting 2-[{4-(3-methoxypropoxy)-3-methylpyridine-2-yl}methylthio]-1H-benzimidazole with an oxidizing agent and removing the unreacted sulfide compounds and sulfone impurities from the medium by means of an extraction and two additional crystallization steps. The unreacted compounds are removed with the organic layer of said extraction step whereas the impurities are removed with the additional crystallization steps wherein rabeprazole free base and impurities are treated in the same phase. Preparation of rabeprazole sodium salt is also covered within the scope of the present invention. Product of the previous crystallization steps is dissolved in methanolic sodium hydroxide and obtained solution is concentrated. Sodium salt of rabeprazole is precipitated by way of adding the residue into diethyl ether. Both rabeprazole and its sodium salt are obtained with sulfone impurity percentage around 0.08 %.