Methanamine, N-methoxy-, hydrochloride (1:1) → 1-benzyl-N-methoxy-N-methylpiperidine-4-carboxamide

Participants

Reaction Steps

A solution of ethyl 1-benzylpiperidine-4-carboxylate (10.0 g, 40.4 mmol) and N,O-dimethylhydroxylamine hydrochloride (6.12 g, 62.6 mmol) in THF (80 mL) was cooled to 0° C. prior to the addition of i-PrMgCl (121.2 mmol, 60.6 mL, 2 M in THF) dropwise. The reaction was stirred for 1 h, then quenched by addition of saturated aqueous ammonium chloride (90 mL). The aqueous and organic layers were separated. The separated aqueous phase was further extracted with ethyl acetate. The combined organic layers were washed with saturated aqueous sodium chloride, dried over MgSO4, and concentrated in vacuo. The residue was chromatographed on silica gel (2-18% methanol in dichloromethane) to afford the desired product (8.88 g, 84%). Rf 0.45 (10% MeOH/CH2Cl2). 1H NMR (CDCl3, 300 MHz) δ 7.40-7.20 (m, 5H), 3.69 (s, 3H), 3.51 (s, 2H), 3.17 (s, 3H), 2.94 (d, 2H, J=11.4 Hz), 2.63-2.66 (m, 1H), 2.01 (td, J=11.7, 2.9 Hz, 2H), 1.83 (qd, J=12.8, 3.7 Hz, 2H), 1.72-1.67 (m, 2H). ESI MS found for C15H22N2O2 m/z [263.3 (M+1)].

Provenance & Evidence