Chloroform → 3,3-dichloro-2-piperidinone

Temperature

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).

1. customthe resulting reaction mixture
2. temperaturebefore being warmed up
3. temperatureto reflux for 2 h
4. temperaturethe reaction mixture was cooled down to 5-10° C.
5. stirringThe resulting mixture was stirred at 0-5° C. for 1 h
6. temperaturebefore being gradually warmed up to room temperature for 12 h
7. customThe two layers were separated
8. extractionthe aqueous layer was extracted with CH2Cl2 (4×50 mL)
9. washThe combined organic extracts were washed with saturated NaCl aqueous solution (50 mL)
10. dry with materialdried over MgSO4
11. concentrationconcentrated in vacuo
12. additionThe residual solids were treated with 30% EtOAc/hexane (50 mL)
13. filtrationbefore being collected by filtration
14. customThe crude pale-yellow solids were dried in vacuo at 30-35° C. for 12 h

ORD record

ord-cd40f2aa350a4a0ba0217c3a38ce4737

Source dataset

uspto-grants-2005_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06919451B2