(S)-3-羟基四氢呋喃的合成工艺优化

Synthetic Process Optimization of (S)-3-Hydroxytetrahydrofuran

对(S)-3-羟基四氢呋喃(1)的产业化合成工艺进行了改进。在乙醇溶剂中,起始原料(S)-4-氯-3-羟基丁酸乙酯(2)经硼氢化钠还原得到(S)-4-氯-1,3-丁二醇(3)。反应完毕后,淬灭反应,过滤后蒸除溶剂,直接投入下一步反应,以水为溶剂加热环合,后处理采用连续萃取的方式,再经减压蒸馏分离、纯化得1,总收率76.2%,纯度99.8%,ee值大于99.8%。改进后的工艺成本低、生产过程安全,适合工业化生产。

The industrial synthetic process of (S)-3-hydroxytetrahydrofuran was improved.(S)-4-Chloro-1,3-butanediol(3) was obtained by reduction of the starting material, ethyl (S)-4-chloro-3-hydroxybutyrate(2), with sodium borohydride in ethanol. The reaction mixture was quenched, followed by evaporation of the solvent. Then, the system was directly heated to give the title compound by ring-closure in water. The continuous extraction was used in the work-up so that the extraction efficiency was improved. After the distillation in vacuum and purification, 1 was obtained in a yield of 76.2% with 99.8% of chemical purity and the ee value greater than 99.8%. The improved synthetic process was lowcost and safe, which was suitable for industrial production.