Potassium Carbonate → Tert-butyl 4-(((4'-cyano-5-(trifluoromethyl)biphenyl-3-yl)methoxy)methyl)-4-(5-fluorobiphenyl-2-yl)piperidine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

A mixture of tert-butyl 4-(2-bromo-4-fluorophenyl)-4-(((4′-cyano-5-(trifluoromethyl)biphenyl-3-yl)methoxy)methyl)piperidine-1-carboxylate (100 mg, 0.15 mmol), phenyl boronic acid (19 mg, 0.15 mmol), potassium carbonate (43 mg, 0.31 mmol) and tetrakis(triphenylphosphine)palladium(0) (18 mg, 0.15 mmol) were placed in a sealable vessel and degassed with nitrogen for 5 min. The vessel was then sealed and heated at 120° C. for 3 h. The reaction was poured into brine (20 mL) and extracted with ethyl acetate (4×5 mL). The combined organic layers were dried (MgSO4) and evaporated to dryness. The resulting residue was purified by chromatography on SiO2 with a ethyl acetate/hexanes gradient from 12% to 100%. The product tert-butyl 4-(((4′-cyano-5-(trifluoromethyl)biphenyl-3-yl)methoxy)methyl)-4-(5-fluorobiphenyl-2-yl)piperidine-1-carboxylate (39 mg, 39%) was isolated as a clear oil. 1H-NMR (CDCl3, 400 MHz) δ 7.68-7.76 (m, 3H), 7.55 (d, J=8.4 Hz, 2H), 7.44 (m, 3H), 7.18-7.28 (m, 3H), 7.03 (m, 1H), 6.94 m, 2H), 6.67 (m, 1H), 4.52 (s, 2H), 3.52 (m, 2H), 3.47 (s, 2H), 2.90 (m, 2H), 1.91 (m, 2H), 1.45 (m, 2H), 1.38 (s, 9H). Mass spec.: 645.2 (M+H).

Provenance & Evidence