Described is a new, practical, and one-pot process, based on the Forster reaction, for the synthesis of cinacalcet hydrochloride (1), a calcimimetic agent and calcium-sensing receptor antagonist. The synthesis comprises the condensation of (1R)-(+)-1-naphthylethyl amine (2) with benzaldehyde (3) followed by reaction of obtained Schiff’s base 4 with 1-(3-halopropyl)-3-(trifluoromethyl)benzene (5) to provide highly unstable iminium salt 6. Subsequent hydrolysis of 6 with water in the same pot yielded cinacalcet. The treatment of cinacalcet with hydrochloric acid during the workup process furnished 1 with an overall yield of around 60%. Our synthetic approach for 1, discussed in this report demonstrates industrial application of the century-old, unexplored name reaction, “Forster’s Reaction” or Forster−Decker synthesis.
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