四氢糠酸的拆分工艺改进

Process Improvement on Resolution of Tetrahydrofuran-2-carboxylic Acid

利用非对映异构体盐在溶剂中溶解度的不同,以(1S,2R)-1-氨基-2-茚醇(1)为手性拆分剂,拆分四氢糠酸[(RS)-THFA,(RS)-2]获得高光学纯的(S)-2,其结构经~1H NMR,^(13)C NMR和HPLC确证。探究了不同溶剂量和投料比对拆分效果的影响。结果表明较佳拆分条件为:以4-甲基-2-戊酮(3)作溶剂,n[(RS)-2]∶n(1)=2.2∶1,一次拆分得91.7%ee(S)-2;再以n[91.7%ee(S)-2]∶n(1)=6∶5进行二次拆分得99.0%ee(S)-2。拆分剂的回收率提高至92.0%,同时对拆分母液中的非目标对映体成功地进行消旋化,回收率为89.0%,实现了四氢糠酸的循环拆分。

（S）-tetrahydrofuran-2-carboxylic acid [ （S）-2 ] with high optical purity was resolved according the different dissolution of the diastereomeric salt, from rac-tetrahydrofuran-2-carboxylic acid [ （RS） -THFA, （ RS ） -2 ] using （ 1S, 2R） -1-aminoindan-2-ol （ 1 ） as the resolving agent. The influences of amount of solvent, the percentage of THFA and the resolving agent to the resolution were stud- ied. The optimum resolution conditions were as follows ： using 4-methylpentan-2-one （3） as solvent, n [（RS）-2] ：n（1）= 2.2：1, the first resolution turns out 91.7% ee （S）-2. 99.0% ee （S）-2 was prepared by second resolution with n [ 91.7% ee （S）-2 ] ：n （1） of 6：5. The recycling resolution was realized with the recovery of 92.0% of the resolving agent as well as 89.0% of THFA which was race- mized by the non target enantiomeric isomer from mother liquor.