N-methylpiperazine (30 mmol, 3.3 mL), 4 mL of 25% NaOH solution, and 40 mL of acetone were added to a 100 mL round-bottomed flask under ice bath cooling conditions. Subsequently, 1-bromo-3-chloropropane (30 mmol, 3 mL) was added and stirred in an ice bath until the reaction was complete, ensuring that all insoluble material was completely dissolved. The reaction mixture was allowed to stand at room temperature for 24 hours. Upon completion of the reaction, the solvent was removed by distillation under reduced pressure. 20 mL of water was added to the residue, which was subsequently extracted with dichloromethane. The organic phase was dried with anhydrous sodium sulfate, filtered and concentrated to give a clarified oil. The reaction flask was placed in an ice bath and 50 mL of ethyl acetate was added. 2.5 mL of concentrated hydrochloric acid was added slowly and dropwise until a large amount of white solid was observed to be produced. During this process, the pH of the reaction system needed to be controlled to be about 2. The solvent was again removed by distillation under reduced pressure and the resulting solid was recrystallized with 100 mL of anhydrous ethanol. Finally, after filtration and drying, 3.3 g of white solid product was obtained as 1-(3-chloropropyl)-4-methylpiperazine dihydrochloride.
