Benzyl Bromide → Ethyl 1-benzylpiperidine-4-carboxylate

Participants

Reaction Steps

Ethyl isonipecotate (40.0 mL, 0.26 mol), K2CO3, (55 g, 0.4 mol) and N,N-dimethylformamide (200 mL) were combined under nitrogen. The resulting mixture was cooled in an ice bath and benzyl bromide (31.0 mL, 0.26 mol) was added. The reaction mixture was allowed to stir overnight with warming to ambient temperature. A saturated aqueous solution of NH4Cl (500 mL) was added, and the product was extracted twice with ethyl acetate (1 L and 0.5 L). The combined organic layers were washed with saturated aqueous NH4Cl (500 mL) and brine (500 mL), dried over Na2SO4, filtered, and concentrated in vacuo. The resulting crude product was purified by flash chromatography on silica gel (400 g) eluting with hexane/ethyl acetate (1:0 to 4:1) to obtain 1-benzyl-piperidine-4-carboxylic acid ethyl ester. 1H NMR (400 MHz, CDCl3) δ ppm 1.24 (t, J=7.07 Hz, 3 H) 1.69-1.82 (m, 2 H) 1.82-1.92 (m, 2 H) 1.96-2.10 (m, 2 H) 2.20-2.34 (m, 1 H) 2.79-2.91 (m, 2 H) 3.48 (s, 2 H) 4.12 (q, J=7.14 Hz, 2 H) 7.20-7.32 (m, 5 H).

Provenance & Evidence