Reaction Steps
4-Methoxy-N-[1-(2′,4,4′-trifluoro-1,1′-biphenyl-2-yl)ethyl]benzamide—A stirred solution of 1-(2′,4,4′-trifluoro-1,1′-biphenyl-2-yl)ethylamine (0.71 g, 2.84 mmol) in dichloromethane (5 mL) was treated with 4-methoxybenzoyl chloride (0.51 g, 3.0 mmol), and N,N-diisopropylethylamine (0.77 g, 6.0 mmol). The reaction was stirred at room temperature for twelve hours, and the solvent evaporated in vacuo to a crude oil. The crude oil was purified by preparative liquid chromatography on a Biotage® 40 Mi column of pre-packed silica gel (90 g), eluting with a gradient of between 5% and 50% methyl tert-butyl ether in hexane at a flow rate of 40 mL/min to afford, after evaporation of the solvent, a colorless oil. Crystallization of the colorless oil from ethyl acetate-hexane yielded the title compound (0.98 g, 2.54 mmol, 90%) as a homogeneous, colorless, crystalline solid, m.p. 163-165° C.; MS [(+ESI), m/z]: 386 [M+H]+; IR (Solid), vmax: 3257, 1620, 1606, 1503, 1329, 1249, 1175, 1032, 844, 777, 670 cm−1; 1H NMR (400 MHz, DMSO-d6) δ: 1.29 (d, J=5.4 Hz, 3H), 3.80 (s, 3H), 4.93 (broad s, 1H), 6.93 (d, J=8.8 Hz, 2H), 7.14 (td, J=8.5, 2.7 Hz, 1H), 7.22 (dd, J=8.5, 5.9 Hz, 2H), 7.37 (t, 2H), 7.46 (d, J=9.1 Hz, 1H), 7.61 (d, J=4.7 Hz, 1H), 7.83 (d, J=7.2 Hz, 2H), 8.66 (d, J=3.9 Hz, 1H), exists as approximate 2:1 mixture of rotamers; Anal. calcd for C22H18F3NO2: C, 68.57; H, 4.71; N, 3.63. Found: C, 68.65; H, 4.80 N, 3.48.
