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

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Reaction Steps

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))

Provenance & Evidence