3-fluoro-4-methoxypropiophenone

1649-96-3

586-22-1

To a stirred dichloromethane (CH2Cl2, 40 mL) solution of dimethyl sulfoxide (DMSO, 7.60 mL, 107 mmol) was slowly added a dichloromethane (CH2Cl2, 20 mL) solution of oxaloyl chloride ((COCl)2, 6.20 mL, 72.3 mmol) at -78 °C. After keeping stirring at -78 °C for 0.25 h, a dichloromethane (CH2Cl2, 40 mL) solution of α-ethyl-3-fluoro-4-methoxybenzenemethanol was slowly added, and stirring was continued for 0.5 h at -78 °C. Subsequently, triethylamine (Et3N, 18.0 mL, 129 mmol) was added at -78 °C and the reaction mixture was gradually warmed up to room temperature over a period of 1 hour. Upon completion of the reaction, the reaction was quenched with water and the mixture was extracted with ethyl acetate (EtOAc). The organic layer was washed sequentially with water and brine, dried over anhydrous sodium sulfate (Na2SO4) and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: n-hexane/ethyl acetate = 15:1) to afford 1-(3-fluoro-4-methoxyphenyl)propan-1-one (3.88 g, 21.3 mmol, 66% yield) as a white solid.1H NMR (400 MHz, CDCl3) δ: 1.22 (3H, t, J = 7.3 Hz), 2.94 (2H , q, J = 7.3 Hz), 3.96 (3H, s), 7.00 (1H, t, J = 8.6 Hz), 7.69-7.77 (2H, m).