Dimethylformamide → 2-Hydroxy-4-methoxybenzonitrile

Participants

Reaction Conditions

Reaction Steps

Zinc cyanide (1.282 g, 0.770 mmol) and 2-bromo-5-methoxy-phenol (3 g, 14.18 mmol) were taken into dimethylformamide (15 mL) and the mixture was degassed with argon for 45 min. To this was added tetrakis(triphenylphosphine)palladium (993 mg, 0.852 mmol), and the reaction mixture was sealed after being degassed for 30 min. After heated at 95° C. for 2 d, the reaction mixture was cooled to room temperature and worked up with water and diethyl ether. The ethereal extracts were washed with brine and dried over anhydrous sodium sulfate. The solid was then filtered off, and the filtrate was concentrated in vacuo. Purification of the crude residue by flash chromatography (Biotage system, KP-Sil™ 32-63 μm, 60 Å silica gel) eluting with 0-25% ethyl acetate in hexanes yielded 2-hydroxy-4-methoxy-benzonitrile (334 mg, 16%).

Provenance & Evidence