4-Chloro-N-methylpiperidine

931-20-4

103057-10-9

5570-77-4

To an anhydrous tetrahydrofuran (THF, 7 mL) solution of diisopropylamine (1.078 mL) was slowly added n-butyllithium (3.08 mL, 2.5 M) dropwise at 0 °C. The reaction solution was stirred at 0 °C for 40 min and then cooled to -23 °C. Subsequently, N-methyl-2-piperidone (0.80 mL) was added to the reaction system and stirred at -23°C for 0.5 hr, after which stirring was continued at -78°C for 1 hr. Next, a solution of anhydrous THF (14 mL) of 4-chloromethyl-N-tritylimidazole (2.70 g) was added dropwise to the above mixture. The reaction mixture was stirred at -78 °C for 4 hours, followed by slow warming to room temperature and stirring overnight (16 hours). Upon completion of the reaction, water and ethyl acetate were added to the mixture and the organic layer was separated after vigorous shaking. The aqueous layer was extracted several times with ethyl acetate and the combined organic layers were washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated to give the crude product. The crude product was purified by fast chromatography (eluent: dichloromethane solution of saturated methanol with 1% to 2% ammonia) to afford the target compound N-methyl-4-chloropiperidine (1.58 g, 52% yield).