Chloroacetyl chloride → 1-(2-chloroacetyl)-N-(1,1-dimethylethyl)-4-piperidinecarboxamide

Temperature

2.5 °C

A solution of N-(1,1-dimethylethyl)-4-piperidinecarboxamide (201 g, 1.0 mol) in dichloromethane (1 L) was cooled under nitrogen to −5° C., and chloroacetyl chloride (124 g, 1.1 mol) in 300 mL of dichloromethane was added dropwise over 30 minutes while maintaining the reaction mixture at 0 to 5° C. Then 20% aqueous potassium carbonate solution (450 g, 0.65 mol) was added dropwise over 30 minutes while keeping reaction temperature between 0 and 5° C. The reaction mixture was stirred for an additional 30 minutes at 0° C., and then allowed to warm to room temperature. The layers were separated, and the aqueous layer was extracted with dichloromethane (200 mL). The combined dichloromethane layers were concentrated under reduced pressure to yield a solid, which was triturated with 400 mL of hexanes. The slurry was filtered, and the filter cake was washed with 100 mL of hexanes and dried in a vacuum oven overnight at 50° C. to give 185.5 g of 1-(2-chloroacetyl)-N-(1,1-dimethylethyl)-4-piperidinecarboxamide as a solid, melting at 140.5-141.5° C.

1. customreaction temperature between 0 and 5° C
2. temperatureto warm to room temperature
3. customThe layers were separated
4. extractionthe aqueous layer was extracted with dichloromethane (200 mL)
5. concentrationThe combined dichloromethane layers were concentrated under reduced pressure
6. customto yield a solid, which
7. customwas triturated with 400 mL of hexanes
8. filtrationThe slurry was filtered
9. washthe filter cake was washed with 100 mL of hexanes
10. customdried in a vacuum oven overnight at 50° C.

ORD record

ord-125448edfa684264ab8a16ab3c84139f

Source dataset

uspto-grants-2014_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08642634B2