Thiophosgene → 5-Chloro-2-(1-(3-fluoro-5-(trifluoromethyl)phenyl)-1-isothiocyanato-2-phenylethyl)pyridine

Participants

Reaction Steps

1-(5-chloropyridin-2-yl)-1-(3-fluoro-5-(trifluoromethyl)phenyl)-2-phenylethanamine (0.132 g, 0.335 mmol) in chloroform (1 mL) was added H2O (1 mL) and NaHCO3 (84 mg, 1.01 mmol). To this vigorously stirred mixture was added thiophosgene (38.3 μl, 0.502 mmol) dropwise. The reaction was stirred at room temperature for 2 hours and diluted with CHCl3 and H2O. The organic layer was separated and washed with brine, dried over MgSO4 and concentrated. The crude mixture was purified by silica gel ISCO chromatography (12 g column) using hexanes/EtOAc (0-30% over 20 min) to give 5-chloro-2-(1-(3-fluoro-5-(trifluoromethyl)phenyl)-1-isothiocyanato-2-phenylethyl)pyridine as a yellow oil (73 mg, 50% yield). LCMS: 4.3 min [M+1] 437.1 (4 min gradient, MeOH/H2O 0.1% TFA); 1H NMR (400 MHz, CDCl3) δ ppm 3.72 (d, J=13.69 Hz, 2H), 4.07 (d, J=13.45 Hz, 2H), 6.89 (dd, J=7.83, 1.47 Hz, 3H), 7.16-7.22 (m, 5H), 7.24 (d, J=1.47 Hz, 1H), 7.37 (dt, J=4.22, 2.17 Hz, 2H), 7.40 (t, J=1.96 Hz, 1H), 7.52 (s, 2H), 7.66 (dd, J=8.31, 2.45 Hz, 2H), 8.65 (d, J=1.96 Hz, 2H).

Provenance & Evidence