Acrylamide → Cinacalcet

Participants

Reaction Steps

Cinacalcet was synthesized by reacting the acrylamide with 1-bromo-3-(trifluoromethyl)benzene using metal catalyzed cross-coupling conditions. In one embodiment, N—((R)-1-naphthalen-1-yl-ethyl)-acrylamide (1.0 equiv.; 0.44 mmol; 100 mg), palladium (II) acetate (5 mol %; 4.9 mg), tri-o-tolylphosphine (0.1 equiv.; 0.44 mmol; 13.4 mg) were suspended in acetonitrile (25 mL). To this suspension was added 1-bromo-3-(trifluoromethyl)benzene (1.0 equiv.; 0.44 mmol; 99 mg) and triethylamine (30 equiv.; 13.2 mmol; 1.8 mL) via syringe. The reaction was heated at reflux for 16 hours to afford (E)-N—((R)-1-Naphthalen-1-yl-ethyl)-3-(3-trifluoromethyl-phenyl)-acrylamide as the product. Solution yield: 79%. Confirmed identity by RRT and LC/MS (M+1): 370.4.

Provenance & Evidence