An Improved Process for the Production of Lansoprazole: Investigation of Key Parameters That Influence the Water Content in Final API

Abstract

An improved large-scale synthesis of lansoprazole 1 an anti-ulcer drug is described. The synthesis commences with condensation of 2-mercaptobenzimadazole 3 with 2-chloromethyl-3methyl-4-(2, 2, 2-trifluoro ethoxy) pyridine hydrochloride 2 using water as a solvent to yield thioether 4. Subsequently, 4 was selectively oxidized to 1 by using sodium hypochlorite, a mild, economic, and eco-friendly oxidizing agent. A systematic investigation of crystallization parameters in the final stage, which enabled us to control the water content in the final API to <0.10%, were also discussed. (As recommended by USP 28 monograph (The United States Pharmacopeia: USP 28: NF 23, 28th rev. of The Pharmacopeia of the U.S., 23rd ed. of The National Formulary; United States Pharmacopeial Convention; Rockville, MD, 2005; p 1110.)