手性气相色谱法拆分4-丙基-二氢呋喃-2-酮对映异构体

Chiral gas chromatography for the separation of the enantiomers of 4-propyldihydrofuran-2(3H)-one

开发了一种用于手性医药中间体4-丙基-二氢呋喃-2-酮对映异构体拆分的气相色谱方法。该对映异构体的R构型是合成抗癫痫药布瓦西坦的关键中间体。采用Rt-bDEXsa手性气相色谱柱分离,氢火焰离子化检测器检测。在优化条件下,(R)-4-丙基-二氢呋喃-2-酮和(S)-4-丙基-二氢呋喃-2-酮可在16 min内分离,且分离度大于1.5。在0.2~10.0 mg/L范围内线性关系良好,线性相关系数均大于0.999。两者的检出限均为0.03 mg/L,定量限均为0.10 mg/L。(R)-4-丙基-二氢呋喃-2-酮和(S)-4-丙基-二氢呋喃-2-酮的加标回收率分别为100.0%~111.3%和99.5%~108.9%,相对标准偏差(RSDs)分别为0.72%~2.1%和0.10%~0.77%。该方法可为4-丙基-二氢呋喃-2-酮对映异构体的拆分提供参考。

A gas chromatography method has been developed for the enantiomeric separation of 4-propyldihydrofuran-2(3H)-one,which is a chiral intermediate in pharmaceuticals.The R configuration of this enantiomer is a crucial intermediate in the synthesis of the anti-epileptic drug,brivaracetam.The method utilized the Rt-bDEXsa chiral gas chromatography column for separation and hydrogen flame ionization detector for detection.Under the optimized conditions,(R)-4-propyldihydrofuran-2(3H)-one and(S)-4-propyldihydrofuran-2(3H)-one can be rapidly separated within 16 min,and the resolution was greater than 1.5.The linear relationships were good within the range of 0.2-10.0 mg/L,and the linear correlation coefficients were greater than 0.999.The detection limits and quantification limits were both 0.03 mg/L and 0.10 mg/L,respectively.The spiked experimental results showed that the recoveries of(R)-4-propyldihydrofuran-2(3H)-one and(S)-4-propyldihydrofuran-2(3H)-one were 100.0%-111.3%and 99.5%-108.9%,respectively,and the relative standard deviations(RSDs)were 0.72%-2.1%and 0.10%-0.77%,respectively.This method provides a reference for the enantiomeric separation of 4-propyldihydrofuran-2(3H)-one.