Effective Synthetic Route for Large Scale Synthesis of Fluphenazine Hydrochloride and process related unknown impurity

Abstract

A new synthetic route has been developed on a large scale for the synthesis of fluphenazine hydrochloride. We started the synthesis with the cheap and readily available tert-butyl piperazine-1-carboxylate and 1- bromo-3-chloropropane.This approach is scalable nucleophilic substitution reaction between tert-butyl piperazine-1-carboxylate and 1-bromo-3- chloropropane to afford tert-butyl 4-(3-chloropropyl) piperazine-1-carboxylate, the resulting amino chloro compound was used for N-alkylation with 2- (trifluoromethyl)-10H-phenothiazine and the obtained N- alkylated product was deprotected and then Nalkylated with chloro ethanol to afford fluphenazine hydrochloride. During the synthectic approach, we identified unknown impurity which was properly isolated and analysed by spectral data. Our synthetic strategy is very effective for large scale synthesis of fluphenazine hydrochloride.