Chloroform → 3,3-Dichloropiperidin-2-one

온도

2.5 °C

A solution of piperidin-2-one (42, 25.0 g, 252.2 mmol) in CHCl3 (250 mL) was treated with PCl5 (158 g, 756.5 mmol, 3.0 equiv) at 0-5° C., and the resulting reaction mixture was stirred at 0-5° C. for 10 min before being warmed up to reflux for 2 h. When HPLC showed the reaction was complete, the reaction mixture was cooled down to 5-10° C. before being transferred into an ice water (500 mL) with caution. The resulting mixture was stirred at 0-5° C. for 1 h before being gradually warmed up to room temperature for 12 h. The two layers were separated, and the aqueous layer was extracted with CH2Cl2 (4×50 mL). The combined organic extracts were washed with saturated NaCl aqueous solution (50 mL), dried over MgSO4, and concentrated in vacuo. The residual solids were treated with 30% EtOAc/hexane (50 mL) before being collected by filtration. The crude pale-yellow solids were dried in vacuo at 30-35° C. for 12 h to afford the desired 3,3-dichloro-piperidin-2-one (43, 27.96 g, 42.36 g theoretical, 66%) as bright-yellow oil, which solidified upon standing at room temperature in vacuo. For 43, CIMS m/z 166/170 (M+−H, C5H7Cl2NO).