A solution of 1-benzylpiperidin-4-one (60 g, 0.3 mol) in THF (100 mL) was slowly added dropwise to a tetrahydrofuran (THF, 600 mL) suspension of NaH (15 g, 0.38 mol, 60% dispersed in mineral oil) at 0 °C. After the dropwise addition was completed, the reaction mixture was continued to be stirred at 0 °C for 30 min. Subsequently, methyl iodide (67 g, 0.47 mol) was added to the reaction system and the reaction mixture was warmed to 60 °C and stirred overnight. After completion of the reaction, the mixture was cooled to room temperature and filtered to remove insoluble impurities. The filtrate was washed with water and subsequently extracted with ethyl acetate (EtOAc, 3 x 300 mL). The organic phases were combined, dried over anhydrous sodium sulfate (Na2SO4) and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (eluent: petroleum ether (PE):ethyl acetate (EtOAc) = 5:1) to afford 1-benzyl-3-methylpiperidin-4-one (30 g, 47% yield) as a yellow oil.1H NMR (400 MHz, DMSO-d6): δ 7.20-7.35 (m, 5H), 3.58 (s, 2H) 2.95-3.02 (m, 2H), 2.48-2.62 (m, 2H), 2.26-2.32 (m, 1H), 2.10-2.18 (m, 1H), 2.00 (q, 1H), 0.81 (d, 3H).
