A modified method for obtaining betahistine hydrochloride

Abstract

The aim of this work was to synthesize betahistine hydrochloride of a satisfactory purity in the highest possible yield. The synthesis consisted of four steps; condensation of paraformaldehyde and 2-methylpyridine yielding 2-(2-pyridyl)ethanol (2) in a yield of at least 26.6%, achieved thanks to a specially developed treatment of the reaction mixture and recycling; dehydration of compound 2 with acetic anhydride under reflux, rendering 2-vinylpyridine (3) in a yield of 72%; addition of methyl amine to the double bond of compound 3, giving betahistine (4) in a yield of 62.5% and finally, preparation of betahistine hydrochloride from betahistine and gaseous hydrochloride in absolute ethanol in a yield of 73%.