165 mL (2 mol) of tetrandrine, 67 mL (1 mol) of 3-chloro-1-propanol and 200 mL of toluene were added sequentially to the reaction flask. The reaction mixture was heated to reflux temperature and maintained for 3 hours. Upon completion of the reaction, it was cooled to room temperature and the solid product was isolated. The solid was collected by diafiltration and the filter cake was washed with 20 mL of toluene. The temperature of the filtrate was controlled at about 75°C and 200 mL of thionyl chloride was slowly added dropwise. After the dropwise addition, the reaction was refluxed for 2 hours. At the end of the reaction, the mixture was cooled to room temperature and subsequently concentrated to dryness under reduced pressure. The resulting residue was recrystallized from anhydrous ethanol to give 105 g of the final white solid product N-(3-chloropropyl)pyrrole hydrochloride in 62.3% yield with a melting point of 169-173°C.
