Water → 1-(2-Chloroacetyl)piperidine-4-carbonitrile

Temperature

55 °C

To a solution of 1-(2-chloroacetyl)-N-(1,1-dimethylethyl)-4-piperidinecarboxamide (26.1 g, 0.10 mol) in N,N-dimethylformamide (35 mL) was added phosphorus oxychloride (18.8 g, 0.123 mol) dropwise over 30 minutes while allowing the temperature of the reaction mixture to rise to 37° C. The reaction mixture was heated at 55° C. for 1 h and then was slowly added to water (about 150 g) cooled with ice to maintain a temperature of about 10° C. The pH of the reaction mixture was adjusted to 5.5 with 50% NaOH aqueous solution. The mixture was extracted with dichloromethane (4×100 mL), and the combined extract was concentrated under reduced pressure to give 18.1 g of the title compound as a solid. This compound was of sufficient purity to use in subsequent reactions.

1. customto rise to 37° C
2. temperaturecooled with ice
3. temperatureto maintain a temperature of about 10° C
4. extractionThe mixture was extracted with dichloromethane (4×100 mL)
5. extractionthe combined extract
6. concentrationwas concentrated under reduced pressure

ORD record

ord-25a615bb7d274128b9fc309971691542

Source dataset

uspto-grants-2014_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08642634B2