Dimethylformamide → 4-Acetyl-2-chloro-5-hydroxybenzonitrile

Participants

Reaction Conditions

Reaction Steps

1-(4-bromo-5-chloro-2-hydroxyphenyl)ethanone (6.2 g, 25 mmol) was combined with zinc cyanide (4.4 g, 37 mmol) in N,N-dimethylformamide (40 mL) degassed with nitrogen and tris(dibenzylideneacetone)dipalladium(0) (0.38 g, 0.42 mmol) and (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (0.57 g, 0.99 mmol) were added. The reaction was degassed with nitrogen and heated to 120° C. and monitored by LC/MS. After heating for 2 hrs, the reaction was allowed to cool to room temperature, diluted with ethyl acetate, and filtered to remove the solids. The organic layer was washed with water, brine, dried over magnesium sulfate and concentrated in vacuo to give the crude product. The product was purified by FCC on silica gel eluting hexane:ethyl acetate gradient to give 4-acetyl-2-chloro-5-hydroxybenzonitrile as a yellow crystalline solid (3.5 g, 72%).

Provenance & Evidence