Synthesis
General procedure: 160 g (1.016 mol) of 1-bromo-3-chloropropane was added to the reactor at a temperature of 20±5°C with constant stirring. 86.1 g (1.011 mol) of piperidine was slowly added dropwise over a period of 2-3 hours. After completion of the dropwise addition, the reaction was continued with stirring for 1 hour. Subsequently, 100 mL of 30% sodium hydroxide solution was added and the reaction was continued for 4 hours. Upon completion of the reaction, a liquid-liquid separation was carried out and the organic phase was dried over anhydrous sodium sulfate. Finally, 127 g of 1-(3-chloropropyl)piperidine was obtained in 78.56% yield.
References
[1] Patent: CN104447620, 2016, B. Location in patent: Paragraph 0053-0055
[2] Patent: CN106749101, 2017, A. Location in patent: Paragraph 0037; 0038
[3] Bioorganic and Medicinal Chemistry Letters, 2011, vol. 21, # 8, p. 2394 - 2399
[4] Bioorganic and Medicinal Chemistry Letters, 2016, vol. 26, # 19, p. 4666 - 4670
[5] Pharmazie, 1980, vol. 35, # 2, p. 69 - 72
