The general procedure for the synthesis of the target compound using 1-(3,4-dimethoxybenzyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline hydrochloride as raw material was as follows: 20 g of 1-(3,4-dimethoxybenzyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline hydrochloride was dissolved in 400 mL of distilled water, and stirred until completely dissolved. Subsequently, ammonia was added to the solution to adjust the pH, and after observing that no white oily material precipitated, 400 mL of toluene was added and mixed with thorough stirring. The organic phase (toluene layer) and the aqueous phase were separated to ensure that there was no residual raw material in the aqueous phase. The organic phase was dried with anhydrous sodium sulfate to obtain 17.3 g of racemate. The racemate was dissolved in 173 mL of acetonitrile and heated to 70 °C. 3.93 g of the splitting agent N-acetyl-D-leucine was slowly added and the reaction was stirred for 20 minutes. Next, 0.522 g of the splitting agent N-acetyl-D-phenylalanine was added and the reaction was continued with stirring for 35 minutes. Upon completion of the reaction, it was slowly cooled to room temperature and subsequently stored in a refrigerator at 4°C for 24 hours to promote crystallization. Upon completion of crystallization, the solid product was collected by filtration. The product was converted to hydrochloride form, treated by adding appropriate amount of hydrochloric acid and dried to give 8.325 g of 1-(3,4-dimethoxybenzyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline hydrochloride in R-configuration. The total yield was 83.25% and the purity was 97.6%.
