Dimethylacetamide → 4-(4-Aminobenzoyl)benzonitrile

Participants

Reaction Conditions

Reaction Steps

A mixture containing (4-aminophenyl)(4-chlorophenyl)methanone (2.5 g, 11 mmol, Intermediate 16: step b), zinc cyanide (1.65 g, 14.0 mmol), tris(dibenzylideneacetone)dipalladium (692 mg, 0.755 mmol), zinc powder (141 mg, 2.16 mmol), 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (XPhos, 371 mg, 0.755 mmol), and dimethylacetamide (54 mL, sparged with nitrogen for 45 minutes) was heated to 120° C. After 2 hours, the flask was allowed to cool to 23° C. The mixture was diluted with ethyl acetate (150 mL) and then filtered through Celite®. The filtrate was washed with saturated aqueous sodium chloride solution (2×100 mL). The organic phase was dried over sodium sulfate and then filtered. Silica gel (8 g) was added to the filtrate and the solvent was removed by rotary evaporation to afford a free-flowing powder. The powder was loaded onto a column of silica gel for purification. Elution with dichloromethane initially, grading to 5% methanol-dichloromethane provided the title compound as a solid.

Provenance & Evidence