Dimethylformamide → 5-Hydroxymethyl-2,4-dimethoxy-benzonitrile

Participants

Reaction Conditions

Reaction Steps

To a solution of (5-bromo-2,4-dimethoxy-phenyl)-methanol (2.75 g, 11.13 mmol) in dimethylformamide (15 mL) at room temperature was added zinc cyanide (784 mg, 6.678 mmol). The reaction mixture was degassed by passing argon through for 2 h before tetrakis(triphenylphosphine)palladium (772 mg, 0.668 mmol) was added. The reaction mixture was heated at 90° C. for 12 h. After the reaction mixture was cooled to room temperature, it was diluted with diethyl ether (100 mL) and washed with sodium bicarbonate solution, brine and dried over anhydrous sodium sulfate. The solid was 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 40-50% ethyl acetate in hexanes yielded 5-hydroxymethyl-2,4-dimethoxy-benzonitrile as a white solid (1.089 g, 51%).

Provenance & Evidence