Sodium Carbonate → Benzyl ethyl piperidine-1,3-dicarboxylate

Participants

Reaction Steps

To a solution of ethyl piperidine-3-carboxylate (4 g, 25.4 mmol) in THF (30 mL) and water (30.0 mL) was added Na2CO3 (6.74 g, 63.6 mmol). The resulting suspension was stirred at rt for 20 min. After this time, benzyl carbonochloridate (4.12 g, 24.17 mmol) was added in dropwise. After addition, the stirring solution became milky, then white precipitates formed. After stirring at rt for 2 h, the reaction was partitioned between EtOAc and water. The separated aqueous phase was extracted with EtOAc (2×). The combined organics were washed with water and saturated aqueous NaCl. The organic layer was dried over Na2SO4, filtered and concentrated to dryness. The oily residue was purified using silica gel chromatography (ISCO system) eluting with a gradient of 0-40% EtOAc/Hex. The desired fractions were concentrated to afford the desired product, 1-benzyl 3-ethyl piperidine-1,3-dicarboxylate (5.68 g, 19.50 mmol, 77% yield) as a colorless oil. Anal. Calcd. for C16H21NO4 m/z 291.3, found: 292.1 (M+H)+; 1H NMR (400 MHz, CDCl3) δ ppm 7.41-7.28 (m, 5 H), 5.26-4.97 (m, 2 H), 4.34-4.06 (m, 3 H), 4.06-3.91 (m, 1 H), 3.13 (br. s., 1 H), 2.96-2.81 (m, 1 H), 2.46 (br. s., 1 H), 2.15-1.96 (m, 1 H), 1.78-1.56 (m, 2 H), 1.49 (br. s., 1 H), 1.33-1.17 (m, 3 H).

Provenance & Evidence