肾上腺素的合成工艺研究

Study on the Synthesis Technology of Epinephrine

目的:对肾上腺素合成工艺参数进行了优化研究.方法:以2-氯-3,4-二羟基苯乙酮为起始原料,经胺化、还原、手型拆分合成出L构型的原料药肾上腺素.结果:胺化反应2-氯-3,4-二羟基苯乙酮和N-甲基苄最佳摩尔比为1:1.5,最佳反应温度为(40±2)℃,最佳反应时间为5 h;还原反应Pd/C的最佳用量为苄基肾上腺酮质量的20%,最佳温度为(35±2)℃,最佳反应时间为7 h;手性拆分DL-肾上腺素和拆分剂L-酒石酸最佳摩尔比为1:2.结论:该合成工艺反应条件温和,安全可行,收率高,适合工业化生产.

Objective:The synthesis process parameters of epinephrine were optimized.Methods:L-Epinephrine was synthesized by amination,reduction and chiral resolution from 2-chloro-3,4-dihydroxyacetophenone which as starting material.Results:The optimum molar ratio of 2-chloro-3,4-dihydroxyacetophenone and N-methylbenzyl in amination is 1∶1.5,the optimum reaction temperature is(40±2)℃,and the optimum reaction time is 5 hours.The optimum amount of Pd/C in the reduction reaction process is 20%of the mass of N-benzyl epinephrine,the optimum reaction temperature is(35±2)℃,and the optimum reaction time is 7 hours.The optimum molar ratio of DL-epinephrine and L-tartaric acid in the chiral resolution process is 1∶2.Conclusion:The reaction conditions of the synthesis process are mild,safe and feasible,and the yield is high,which is suitable for industrial production.