Ammonium Hydroxide → Riluzole

Participants

Reaction Steps

To a solution of 4-trifluoromethoxyaniline (Aldrich, 4.83 g, 30 mmol) in 50 mL of AcOH, was added KSCN (Aldrich, 11.64 g, 120 mmol). After the mixture was stirred for 30 min, a solution of bromine (Aldrich, 1.55 mL, 30 mmol) in 20 mL of AcOH was added over 30 min period, and the resulting reaction mixture was stirred overnight. The mixture was diluted with ice/water, brought to pH 8 with conc. NH4OH. The mixture extracted 3× with EtOAc (300 mL). The organic layers were washed twice with a brine solution (300 mL), dried over Na2SO4 and concentrated. The residue was purified by chromatography (40%-45% EtOAc/Hexanes) to give 6.0 g (85%) of product. 1H NMR (400 MHz, DMSO-d6) δ 7.76 (d, J=2.2 Hz, 1H), 7.63 (s, 2H), 7.36 (d, J=8.7 Hz, 1H), 7.17 (dd, J=8.7, 2.4 Hz, 1H), 3.23 (s, 3H). MS (EI): m/z 235 (M+H).

Provenance & Evidence