[Synthesis]
General procedure for the synthesis of 1-benzyl-5-(hydroxymethyl)piperidin-2-one from methyl 1-benzyl-6-oxopiperidine-3-carboxylate: the compound methyl 1-benzyl-6-oxopiperidine-3-carboxylate (5.23 g, 23.85 mmol) was dissolved in anhydrous THF (35 mL) and cooled down to 0 °C. LiBH4 (1.04 g, 47.70 mmol) was added under stirring, followed by slowly warming the reaction mixture to room temperature and stirring overnight. Upon completion of the reaction, the reaction was quenched with water (20 mL) at 0 °C, followed by the addition of 10% HCl solution to adjust the pH. The aqueous layer was extracted with EtOAc (4 x 20 mL), the organic layers were combined, dried with anhydrous MgSO4, filtered and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (eluent: cyclohexane/EtOAc, 60:40) to afford 1-benzyl-5-(hydroxymethyl)piperidin-2-one (4.03 g, 77% yield) as a clear oil (Rf = 0.11, cyclohexane/EtOAc, 50:50).1H NMR (600 MHz, CDCl3) δ 7.33-7.18 ( m, 5H, PhH), 4.59 (d, J = 14.6 Hz, 1H, PhCH2), 4.53 (d, J = 14.6 Hz, 1H, PhCH2), 3.53 (ddd, J = 10.7, 5.6 Hz, 1H, CH2OH), 3.44 (ddd, J = 10.7, 7.2 Hz, 1H, CH2OH), 3.30 ( ddd, J = 12.2, 5.2, 1.5 Hz, 1H, NCH2), 2.99 (dd, J = 12.2, 10.1 Hz, 1H, NCH2), 2.92 (br s, 1H, OH), 2.51 (ddd, J = 17.8, 5.8, 3.4 Hz, 1H, C=OCH2), 2.39 (ddd, J = 17.8, 11.3, 6.5 Hz, 1H, C=OCH2), 2.39 (dd, J = 17.8 11.3, 6.5 Hz, 1H, C=OCH2), 2.04-1.95 (m, 1H, OHCH2CH), 1.89-1.82 (m, 1H, C=OCH2CH2), 1.54-1.46 (m, 1H, C=OCH2CH2); 13C NMR (151 MHz, CDCl3) δ 170.0, 137.0 , 128.5, 127.9, 127.3, 64.3, 50.3, 49.8, 36.4, 31.1, 23.8; HRMS (ES) m/z calcd for C13H18NO2 [M+H]+ 220.1338, found 220.1329. |