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Example 4 Synthesis of 1-(3-chloropropyl)pyrrolidine At 0°C, 186 g (1.18 mol) of 1-bromo-3-chloropropane was dissolved in 200 ml of ether and 2 equivalents of pyrrolidine were slowly added. After addition, the reaction mixture was gradually warmed to room temperature and stirred overnight. Upon completion of the reaction, the resulting white solid was removed by filtration. Ice-cold 10% hydrochloric acid solution was added to the filtrate and the ether layer was discarded after partitioning. The aqueous phase was alkalized with ice-cold 20% sodium hydroxide solution and subsequently extracted with ether. The organic phases were combined and dried over anhydrous sodium sulfate. The ether was evaporated under reduced pressure and the residue was distilled under reduced pressure at 95 °C/30 mmHg to give 91 g of the target product 1-(3-chloropropyl)pyrrolidine as a pale yellow liquid in 53% yield.

[1] Pharmazie, 1980, vol. 35, # 2, p. 69 - 72
[2] Patent: EP1593679, 2005, A1. Location in patent: Page/Page column 27
[3] Patent: US2005/245524, 2005, A1. Location in patent: Page/Page column 27
[4] European Journal of Medicinal Chemistry, 2014, vol. 89, p. 198 - 206
[5] Journal of the American Chemical Society, 1955, vol. 77, p. 2855,2857