To a stirred solution of 4-hydroxyacetophenone (5.0 g, 36.76 mmol) in N,N-dimethylformamide (DMF, 50 mL) was added sodium 2-chloro-2,2-difluoroacetate (6.2 g, 40.44 mmol) followed by sodium hydroxide (NaOH, 1.76 g, 44.11 mmol). The reaction mixture was stirred at 100 °C for 14 hours. After completion of the reaction, the mixture was diluted with cold water and the product was extracted with ethyl acetate (EtOAc). The organic layers were combined, dried with anhydrous sodium sulfate (Na2SO4) and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography using a 20-30% ethyl acetate/hexane solvent mixture to afford the target compound 1-(4-difluoromethoxyphenyl)ethanone (3.5 g, 51.0% yield) as a colorless liquid.1H NMR (400 MHz, DMSO-d6): δ 8.05-8.01 (m, 2H), 7.59-7.22 (m 3H), 2.50 (s, 3H); LC-MS: m/z 187.0 [M+H]+.
