Hydrochloric Acid → 4-Acetyl-2-fluorobenzonitrile

Temperature

90 °C

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.

1. additionwas added
2. temperaturethe reaction mixture was heated at 90° C. for 4 hours
3. temperatureThe reaction mixture was cooled to room temperature
4. extractionextracted with diethyl ether (2×300 mL)
5. washwashed with water and brine
6. dry with materialdried over magnesium sulfate (MgSO4)
7. concentrationconcentrated
8. customto give an oil
9. customThe oil was purified
10. washeluting with ethyl acetate/hexane (1:3)

ORD record

ord-459ae0c3e97d4ddbae6eaeda6c9eee6e

Source dataset

uspto-grants-2004_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06740655B2