消旋正丁基苯酞拆分方法的改进

Improvement of optical resolution of dl-n-butylphthalide

对消旋正丁基苯酞的化学拆分方法进行了改进,提高了终产物的光学纯度和总收率。方法如下:先将消旋正丁基苯酞在氢氧化钠水溶液中开环、酸化,再与拆分试剂——左旋α-苯乙胺反应得到2个非对映异构体胺盐的混合物,然后用丙酮和左旋α-苯乙胺的混合溶液重结晶,得到左旋正丁基苯酞的左旋α-苯乙胺盐,酸性条件下将其解离并环合,减压蒸馏得到左旋正丁基苯酞,并通过对比实验确定了最优化的工艺条件。改进后的拆分方法有效抑制了左旋正丁基苯酞的左旋α-苯乙胺盐在重结晶过程中的热分解,提高了产物左旋正丁基苯酞的光学纯度(>99%ee)和总收率(>25%)。

Chemical resolution of dl-n-butylphthalide is improved to increase the optical purity and yield of the end product. The method is as follows ： dl-n-butylphthalide opens ring in solution of sodium hydroxide and then is acidized with hydrochloric acid. （ ± ）2-（1-hydroxypentyl） benzoic acid is obtained, which then reacts with L-α-phenylethylamine to give the corresponding diastereoisomeric amine salts. The amine salts are recrystallized with aeetone/L-α-phenylethylamine mixed solution to give L-α-phenylethylamine amine of L-n-butylphthalide,and subsequently convert to L-n-butylphthalide via acidifization, cyclization and vacuum distillation. The optimal conditions are determined by the comparative study. Thermal decomposition of L-α-phenylethylamine amine of L-n-butylphthalide in the process of recrystallization is restrained, and the yield （ 〉 25% ） and optical purity （ 〉 99% ee） of the desired product are increased.