3-Trifluoromethylcinnamic acid → 3-(3-Trifluoromethylphenyl)propanoic acid

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Reaction Steps

Tetrahedron letters, (49), 13-15, (2008), discloses a synthetic sequence to Cinacalcet hydrochloride comprising reduction of 3-(trifluoromethyl)cinnamic acid in the presence of palladium hydroxide to obtain 3-(3-trifluoromethylphenyl)-propanoic acid, which is coupled with (R)-1-(1-naphthyl)ethylamine to the corresponding amide. The amide is then reduced in the presence of boron trifluoride-THF and sodium borohydride as reducing agents. After complete conversion, the resulting amine-borane complex is hydrolyzed by the addition of water and the crude Cinacalcet extracted into toluene is reacted with hydrochloric acid to give Cinacalcet hydrochloride, according to the following Scheme 5:

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