左乙拉西坦与卤代扁桃酸共晶的制备及表征

Preparation and characterization of levetiracetam-halogenated mandelic acid cocrystal

为了研究左乙拉西坦共晶拆分分离卤代扁桃酸对映体的可行性,发展共晶拆分技术,通过液体辅助研磨法和冷却结晶法成功制备5种共晶:左乙拉西坦-(S)-2-氯扁桃酸(物质的量比1:1)、左乙拉西坦-(S)-3-氯扁桃酸(物质的量比1:1)、左乙拉西坦-(S)-4-氯扁桃酸(物质的量比1:1)、左乙拉西坦-(S)-4-溴扁桃酸(物质的量比1:2)和左乙拉西坦-(R)-4-氟扁桃酸(物质的量比1:2),并用X射线粉末衍射(XRPD)、差示扫描量热(DSC)、红外光谱(IR)、固体核磁(^(13)C-NMR)和元素分析(EA)对5种共晶进行表征。结果表明,卤素基团不仅影响共晶的构型,还会影响共晶中原料的化学计量比。研究可为共晶拆分法分离外消旋对映体提供支持。

In order to study the feasibility of separation of halogenated mandelic acid enantiomers by levetiracetam cocrystal and develop cocrystal resolution technology, five cocrystals were prepared by liquid-assisted grinding and cooling crystallization: levetiracetam-(S)-2-chloromandelic acid(molar ratio of 1:1),levetiracetam-(S)-3-chloromandelic acid(molar ratio of 1:1), levetiracetam-(S)-4-chloromandelic acid(molar ratio of 1:1), levetiracetam-(S)-4-bromomandelic acid(molar ratio of 1:2) and levetiracetam-(R)-4-fluoromandelic acid(molar ratio of 1:2). X-ray powder diffraction(XRPD), differential scanning calorimetry(DSC), infrared spectroscopy(IR), solid nuclear magnetic resonance(^(13)C-NMR) and elemental analysis(EA) were used to characterize the five cocrystals. The results show that halogen group affects cocrystal configuration and stoichiometric ratio of raw materials in cocrystal. This study is helpful for the separation of racemic enantiomers via co-crystallization.