Thionyl Chloride → Benzyl 4-(chlorocarbonyl)piperidine-1-carboxylate

Participants

Reaction Steps

To a stirred solution of 1-(benzyloxycarbonyl)piperidine-4-carboxylic acid (2.6 g, 10 mmol) in anhydrous dichloromethane (10 mL) was added dropwise thionyl chloride (10 mL) at 0° C. After the addition, the solution was stirred at room temperature overnight, and then the solvent was removed in vacuum to give benzyl 4-(chlorocarbonyl)piperidine-1-carboxylate. Then it was added to a solution of ethyl 3-amino-2-hydroxybenzoate (1.34 g, 8 mmol) and triethylamine (3 g, 30 mmol) in anhydrous dichloromethane (20 mL) at 0° C. After the addition, the mixture was stirred at room temperature overnight. The mixture was diluted with dichloromethane, washed with water (30 mL×3), brine (30 mL), dried over anhydrous sodium sulfate, and concentrated to give a crude product. The crude product was purified by chromatography (silica gel, petroleum ether/ethyl acetate=20:1 to 2:1) to give benzyl 4-(2-hydroxy-3-(methoxycarbonyl)phenylcarbamoyl)piperidine-1-carboxylate (2.63 g, yield 80%). 1H-NMR (400 MHz, CDCl3) δ (ppm): 1.46-1.56 (m, 2H), 1.79-1.82 (d, J=11.6 Hz, 2H), 2.75-2.87 (m, 3H), 3.92 (s, 3H), 4.04-4.07 (d, J=11.2 Hz, 2H), 5.08 (s, 2H), 6.90-6.94 (t, J=8 Hz, 1H), 7.30-7.40 (m, 5H), 7.54-7.56 (m, 1H), 8.09-8.11 (d, J=7.2 Hz, 1H), 9.34 (s, 1H), 10.99 (brs, 1H); LC-MS (ESI) m/z: 413 (M+1)+.

Provenance & Evidence