Hydrochloric Acid → 4-Acetyl-2-fluorobenzonitrile

Participants

Reaction Conditions

Reaction Steps

A mixture of 4-bromo-2-fluorobenzonitrile (5.0 g, 20.0 mmol), butyl vinyl ether (12.5 g, 124.0 mmol), triethylamine (4.0 g, 40.0 mmol) 1,3-bis(diphenylphosphino)propane (453 mg, 1.1 mmol), thallium acetate (5.8 g, 22.0 mmol), and palladium acetate (224 mg, 1.0 mmol) in dry dimethylformamide (50 mL) under nitrogen was heated at 90° C. for 3 hours. An additional charge of 1,3-bis(diphenyl-phosphino)propane (453 mg, 1.1 mmol) and palladium acetate (244 mg, 1.0 mmol) was added and the reaction mixture was heated at 90° C. for 4 hours. The reaction mixture was cooled to room temperature, 25 mL of 2N hydrochloric acid was added, and the reaction mixture was stirred at room temperature for 30 minutes. The reaction mixture was then poured into 300 mL of water and extracted with diethyl ether (2×300 mL). The organic extracts were combined and then washed with water and brine, and thereafter dried over magnesium sulfate (MgSO4) and concentrated to give an oil. The oil was purified using flash chromatography on silica gel, eluting with ethyl acetate/hexane (1:3) to give 2.5 g of 4-acetyl-2-fluoro-benzonitrile final product as an oil.

Provenance & Evidence