GENERAL METHOD: 3-methoxy-4-cyanopyridine (0.88 g, 6.5 mmol) was dissolved in a three-necked flask containing 20 mL of anhydrous tetrahydrofuran under nitrogen protection. The reaction system was cooled to 0 °C to form a homogeneous solution. A tetrahydrofuran solution of methylmagnesium iodide (3 M, 4.3 mL, 12.8 mmol) was added slowly. The reaction was kept stirred at 0 °C for 2 h. The reaction was subsequently quenched with 50 mL of ice water. The pH was adjusted to neutral with 2 N hydrochloric acid, followed by extraction with ethyl acetate (3 x 50 mL). The organic phases were combined, dried with anhydrous sodium sulfate and concentrated under reduced pressure to give the crude product. Purification by silica gel column chromatography (elution gradient: 0-100% ethyl acetate/hexane) afforded the colorless oily product 1-(3-methoxypyridin-4-yl)ethanone (0.79 g, 79% yield). 1-(3-Methoxypyridin-4-yl)ethanone (7c): the reaction was carried out in 10 mL of anhydrous tetrahydrofuran with 3-methoxy-4-cyanopyridine (0.46 g, 3.4 mmol) and tetrahydrofuran solution of methylmagnesium iodide (3 M, 2.24 mL, 6.72 mmol) according to the above general method. The crude product was purified by silica gel column chromatography (eluent: 50% ethyl acetate/50% hexane) to afford the yellow oily target compound (0.38 g, 75% yield). 1H NMR (400 MHz, CDCl3) δ 8.48 (s, 1H), 8.35 (d, J = 4.8 Hz, 1H), 7.49 (d, J = 4.8 Hz, 1H), 4.04 (s, 3H), 2.63 (s, 3H); MS (ESI+): m/z 152 [M+H]+.
