The general procedure for the synthesis of 1-(2-chloroethyl)-4-methylpiperazine dihydrochloride from N-methylpiperazine and 1-bromo-2-chloroethane was as follows: 10 mL of a 25% NaOH solution and 1 mL (9 mmol) of N-methylpiperazine were added sequentially to a dry reaction flask. The mixture was heated to 50 °C and then 1.8 mL (18 mmol) of 1-bromo-2-chloroethane was added slowly and dropwise with stirring. The reaction mixture was kept at 50 °C for 6 hours with stirring. After the reaction was completed, the mixture was cooled to room temperature. The reaction mixture was extracted with ethyl acetate (3 x 20 mL), the organic phases were combined, washed with saturated NaCl solution (20 mL), and then dried over anhydrous Na2SO4. The desiccant was removed by filtration and the filtrate was concentrated to dryness under reduced pressure. A small amount of ethanol/NaOH solution was added dropwise to the residue, and the mixture was shaken and placed in a refrigerator overnight. Finally, the mixture was concentrated to dryness under reduced pressure to give 0.43 g of white solid product in 23% yield. The melting point of the product was 227-230 °C.
