865664-05-7

680610-60-0

75-16-1

865664-05-7

Methylmagnesium bromide (3.0 M, dissolved in ethyl ether (Et2O), 1.82 L, 5.48 mol) was added slowly and dropwise to a tetrahydrofuran (THF, 2.7 L) solution of compound 456A (270 g, 1.37 mol) at -78 °C. The reaction mixture was stirred continuously at -78°C for 1 hour. Subsequently, the reaction was quenched with saturated aqueous ammonium chloride solution (5.0 L) and extracted with ethyl acetate (EtOAc, 2 x 5.0 L). The organic layers were combined, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The crude product obtained was purified by silica gel column chromatography with the eluent being a hexane solution of 10% ethyl acetate to give the final target product 1-(2-fluoro-3-methylphenyl)ethanone (Compound 456B, 200 g, 96% yield). The structure of the product was confirmed by 1H NMR (400 MHz, chloroform-d): δ 7.68-7.64 (m, 1H), 7.37-7.34 (m, 1H), 7.09 (t, J=7.0 Hz, 1H), 2.64 (s, 3H), 2.32 (s, 3H).