Boron tribromide → (S)-N-(1-(5-chloropyridin-2-yl)-1-(3-fluoro-5-hydroxyphenyl)-2-phenylethyl)-4-fluoro-3-(trifluoromethyl)benzamide

Participants

Reaction Conditions

Reaction Steps

To a solution of (S)-N-(1-(5-chloropyridin-2-yl)-1-(3-fluoro-5-methoxyphenyl)-2-phenylethyl)-4-fluoro-3-(trifluoromethyl)benzamide (696 mg, 1.27 mmol, prepared according to procedures 5, 6, 7 and 2) in CH2Cl2 at 0° C. was added BBr3 (12.7 mL, 1M, 12.7 mmol). The mixture was stirred at 0° C. for 3 hrs before it was quenched by being carefully poured into cold Na2CO3 solution. The aqueous was extracted with EtOAc. The combined organic layers were washed with brine, dried over MgSO4, concentrated and the crude mixture was purified by ISCO chromatography (40 g column) using hexanes/EtOAc (0-40% over 25 min) to give (S)-N-(1-(5-chloropyridin-2-yl)-1-(3-fluoro-5-hydroxyphenyl)-2-phenylethyl)-4-fluoro-3-(trifluoromethyl)benzamide as an offwhite solid (606 mg, 90% yield). LCMS: 4.07 min [M+1] 533.30 (4 min gradient, MeOH/H2O 0.1% TFA); 1H NMR (400 MHz, CDCl3) δ ppm 3.64 (d, J=13.21 Hz, 1 H), 4.48 (d, J=12.96 Hz, 1 H), 6.21 (dt, J=10.03, 2.20 Hz, 1 H), 6.45-6.55 (m, 3 H), 6.95-7.04 (m, 3 H), 7.11 (t, J=7.46 Hz, 1 H), 7.20-7.30 (m, 3 H), 7.53 (s, 1 H), 7.70 (dd, J=8.68, 2.32 Hz, 1 H), 7.90 (ddd, J=8.50, 4.46, 2.45 Hz, 1 H), 8.03 (dd, J=6.72, 2.08 Hz, 1 H), 8.29-8.32 (m, 1 H), 9.33-9.41 (m, 1 H).

Provenance & Evidence