论文部分内容阅读
目的建立以托品醇为原料,通过酰化和拆分制备缩瞳新药(1R,3S,5R,6S)-3α-对甲苯磺酰氧基-6β-乙酰氧基莨菪烷盐酸盐[(S)-OTS.HCl]的工艺。方法运用正交试验优化酰化反应条件并改进拆分工艺;通过高效液相色谱(HPLC)法分析产品光学纯度。结果最佳酰化条件为物料配比n(托品醇)∶n(对甲苯磺酰氯)=1∶1.2,室温下反应5 d;优化的拆分条件为n(外消旋OTS)∶n[L-(-)-二苯甲酰酒石酸]=1∶1.2;(S)-OTS.HCl的总产率为25.6%,光学纯度为98.5%。结论此制备工艺简单、稳定、可控,适合工业化生产。
OBJECTIVE To establish a novel drug (1R, 3S, 5R, 6S) -3α-p-toluenesulfonyloxy-6β-acetoxytodanil hydrochloride [ S) -OTS.HCl] process. Methods The orthogonal test was used to optimize the acylation reaction conditions and to improve the resolution process. The optical purity of the product was analyzed by high performance liquid chromatography (HPLC). Results The optimal acylation conditions were as follows: n (p-toluenesulfonyl chloride) = 1: 1.2 at room temperature and 5 d at room temperature. The optimal resolution conditions were n (racemic OTS): n [L - (-) - dibenzoyltartaric acid] = 1: 1.2; The overall yield of (S) -OTS.HCl was 25.6% and the optical purity was 98.5%. Conclusion The preparation process is simple, stable, controllable, suitable for industrial production.