1-(1,4-苯并二噁烷-2-羰基)哌嗪对映体的分离研究

Study of the Enantioseparation of 1-(1,4-Benzodioxane-2-carbonyl)piperazine Enantiomers

1 (1, 4 苯并二口恶烷2 羰基)哌嗪是制备抗高血压药物多沙唑嗪的重要中间体,手性多沙唑嗪可以通过中间体的手性分离来制备。用柱前衍生化-反相高效液相色谱法对1 (1, 4 苯并二口恶烷2 羰基)哌嗪对映体进行了分离。结果表明,用乙酰葡萄糖异硫氰酸酯(GITC)为柱前手性衍生化试剂,C18柱(4 6mm×250mm)为色谱柱,可以将1 (1, 4 苯并二口恶烷2 羰基)哌嗪对映体分离,其他色谱条件为:流动相组成为V(甲醇)∶V(0 02mol/L磷酸二氢钾水溶液) = 53∶47,流速为0 5mL/min,检测波长为250nm。在选择的测定条件下,非对映异构体分离度约等于1 3(R=1 3)。

Benzodioxane-2-carbonyl)piperazine is an important intermediate for the preparation of antihypertensive drug doxazosin.Chiral doxazosin can be synthesized by the enantioseparation of intermediates.A high-performance liquid chromatographic method for the separation of enantiomers of 1-(1,4-benzodioxane-2-carbonyl)piperazine has been developed.The results show that the enantiomers can be separated with 2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl isothiocynate(GITC) as the derivatization reagent and a column of C_(18).Other chromatographic conditions are:mobile phase consisting of methanol and 0.02 mol/L aqueous potassium dihydrogen phosphate solution(53∶47,V/V) at a flow rate 0.5 mL/min and the wavelength for detection set at 250 nm.Under the optimum conditions two diastereoisomers were well separated(R=1.3).