Thionyl Chloride → 1-Acetylpiperidine-4-carbonyl chloride

Participants

Reaction Steps

To 1-acetylisonipecotic acid (41.74 g, 243.8 mmol) was added thionyl chloride (200 mL), and the resulting mixture was stirred for 30 minutes. The mixture was diluted with petroleum ether. The precipitated solid was collected and washed with petroleum ether to afford 1-acetylisonipecotoyl chloride. This was added to a stirring mixture of cumene (120 mL) and aluminium chloride (69.6 g, 522 mmol) and the resulting mixture was stirred at 110° C. for 1 hour. The mixture was poured into ice, and extracted twice with ethyl acetate. The organic layers were combined, washed with brine, a dried over magnesium sulfate, filtered, and concentrated under reduced pressure. To the residue was added concentrated hydrochloric acid (100 mL), and the mixture was refluxed for 12 hours. The mixture was cooled to room temperature and was washed twice with diethyl ether. The aqueous solution was made basic with 8N sodium hydroxide solution and then extracted twice with ethyl acetate. The organic layers were combined, washed with an aqueous saturated sodium hydrogencarbonate, dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was crystallized from ethyl acetate-hexane to obtain the title compound (23.5 g, yield 41%).

Provenance & Evidence