Chloroform → 3,3-Dichloro-5,5-dimethylpiperidin-2-one

To a cold (0° C.) stirred solution of 5,5-dimethyl-2-piperidone (30.2 g, 0.24 mol) in 475 mL of CHCl3, PCl5 (57.1 g, 0.26 mol) was added at such a rate that the temperature never exceeded 7° C. After the addition was complete, stirring was continued for 10 min. Sulfuryl chloride (96.6 g, 0.72 mol) was slowly added and the mixture was heated under reflux for 1 h. The solution was concentrated under reduced pressure. The residue was cooled in ice and diluted with 250 mL of ice-water. The product was then extracted with CHCl3 (6×250 mL) and the organic layer was dried (MgSO4) and filtered. The filtrate was concentrated under reduced pressure. The residue was applied to silica-gel column chromatography, and then the column was eluted with CHCl3-MeOH (50:1). The titled compound was obtained as a white solid (41.3 g, 88.8%). (J. Med. Chem., 20, 1176 (1977))

1. additionwas added at such a rate that the temperature never exceeded 7° C
2. additionAfter the addition
3. temperaturethe mixture was heated
4. temperatureunder reflux for 1 h
5. concentrationThe solution was concentrated under reduced pressure
6. temperatureThe residue was cooled in ice
7. additiondiluted with 250 mL of ice-water
8. extractionThe product was then extracted with CHCl3 (6×250 mL)
9. dry with materialthe organic layer was dried (MgSO4)
10. filtrationfiltered
11. concentrationThe filtrate was concentrated under reduced pressure
12. washthe column was eluted with CHCl3-MeOH (50:1)

ORD record

ord-a5b3f7dc6c884ecc9d02f1d99bfc439c

Source dataset

uspto-grants-2010_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07812014B2