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 23United States Pharmacopeial ConventionRockville, MD20051110.)

An ammonium molybdate deposited amorphous silica coated iron oxide magnetic core–shell nanocomposite for the efficient synthesis of 2-benzimidazoles using hydrogen peroxide

“…2-Benzimidazole and its derivatives are important aromatic nitrogen heterocycles due to their ubiquitous presence and wide applications in many pharmaceutical and biological areas as antiulcer agents, antihypertensives, antivirals, antifungals, anticancer agents, and antihistamines, as well as in organic synthesis. [1][2][3][4][5][6] The widespread interest in 2-benzimidazoles has prompted extensive studies on their synthesis and a series of methods has been subsequently developed in recent decades. The coupling of o-phenylenediamines with carboxylic acids 7 or their derivatives 8 is an established general method to prepare benzimidazoles, but the harsh reaction conditions and relatively low yields limit its applications.…”

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“…Lansoprazole sulphide (LAN30) is the key intermediate for the synthesis of lansoprazole drug substance. The purity of Lansoprazole sulphide determines the quality of lansoprazole drug substance with high yield in the synthetic process during the manufacturing [1][2][3][4][5][6][7][8]. Its molecular formula is C16H14F3N3OS.…”

Application of Continuous Flow Micromixing Reactor Technology for Synthesis of Benzimidazole Drugs

“…Recently we reported an efficient, scalable synthesis of antiulcer drugs ( 1a – 1c ), by employing aqueous sodium hypochlorite (cost: ∼$0.1/kg) in place of expensive m -CPBA (cost: ∼$44/kg) for oxidation of thioether 6a – 6c (Scheme ) . The NaOCl oxidation significantly improved the yield and quality of the sulfoxides, generating only NaCl and H 2 O as by products.…”