Diethyl Ether → (2-Amino-5-chloro-4-fluoro-phenyl)-phenyl-methanone

Participants

Reaction Steps

A solution of phenylmagnesium bromide (7.18 ml, 3M solution in diethyl ether, 21.5 mmol) in diethyl ether (15 ml) was added to a solution of 2-amino-5-chloro-4-fluoro-benzonitrile (1225 mg, 7.18 mmol) in diethyl ether (20 ml) at 0° C. The reaction mixture was then stirred at reflux for 2 h, cooled to room temperature and quenched carefully by addition of 2N HCl (˜40 ml). The mixture was heated to 55° C. for 3 h and then cooled to room temperature again. 3N NaOH (˜20 ml) was added carefully at 0° C. to adjust the pH to 9. The mixture was extracted with EtOAc and the combined extracts were washed with brine, dried with Na2SO4 and evaporated. The remaining residue was purified by column chromatography (silica gel, heptane/EtOAc 95:5-90:10) to afford the title compound (1667 mg, 93%) as yellow solid. MS (ESI): 250.3 (M+H)+.

Provenance & Evidence