Potassium Carbonate → 4-(Difluoromethoxy)benzonitrile

Temperature

95 °C

To a solution of 4-hydroxybenzonitrile (4.76 g, 40 mmol) in 150 mL of DMF was added 5.52 g (40 mmol) of K2CO3. The mixture was heated at 95° C. and 5.27 mL (50 mmol) of CICF2CO2Me was added slowly over 10 minutes. The reaction was stirred at 95 ° C. for 15 minutes and a 1.5 mL portions of ClCF2CO2Me were added until no changes were observed by TLC. The reaction was stirred overnight at room temperature diluted with water (300 mL) and extracted with Et2O. The combined organic layers were washed with brine, dried over MgSO4 and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel (30% ethyl acetate/hexane) to afford the corresponding nitrile as a white solid (3.0 g, 44%).

1. addition5.27 mL (50 mmol) of CICF2CO2Me was added slowly over 10 minutes
2. stirringThe reaction was stirred overnight at room temperature
3. extractionextracted with Et2O
4. washThe combined organic layers were washed with brine
5. dry with materialdried over MgSO4
6. concentrationconcentrated under reduced pressure
7. customThe residue was purified by flash chromatography on silica gel (30% ethyl acetate/hexane)

ORD record

ord-9bbea0cdcd484bb38659ed8b55156612

Source dataset

uspto-grants-2001_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06200993B1