Donepezil Hydrochloride → 2-Pyridin-4-ylmethyl-indan-1-one

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Reaction Steps

U.S. Pat. No. 6,252,081 teaches the preparation of Donepezil HCl by the reaction of 1-indanone derivative with carbonate ester. The resulting 2-alkoxycarbonyl-1-indanone derivative is halogenated with (4-pyridyl)methyl or a salt thereof and decarboxylated successively to give 2-(4-pyridyl)methyl-1-indanone derivative. On reacting the 2-(4-pyridyl)methyl-1-indanone derivative with benzyl bromide, their quarternary ammonium salts are formed, which on reduction with platinum oxide catalyst gives Donepezil HCl (Examples 1 to 3). Overall yield of Donepezil HCl 82% (98%×85%×100%×99%).

Provenance & Evidence