Industrial Application of the Forster Reaction: Novel One-Pot Synthesis of Cinacalcet Hydrochloride, a Calcimimetic Agent

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 (1 R )-(+)-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.