4-苄基-2-[(R)-1-[3,5-二(三氟甲基)苯基]乙氧基]吗啉-3-酮的不对称转化的动态动力学拆分

Synthesis of (R)-4-benzyl-2-((R)-1-(3,5-bis(trifluoromethyl)phenyl)ethoxy)morpholin-3-one and Dynamic Kinetic Resolution of its Asymmetric Transformation

摘要:

以4-苄基-2-羟基吗啉-3-酮为原料，经2步反应制备得到一对非对映异构体4-苄基-2-[(R)-1-[3,5-二(三氟甲基)苯基]乙氧基]吗啉-3-酮，然后以叔丁醇钾为碱环境，利用不对称转化的动态动力学拆分，转化为手性纯(R)-4-苄基-2-[(R)-1-[3,5-二(三氟甲基)苯基]乙氧基]吗啉-3-酮。转化后手性产物与非对映异构体的比例为96:4，在工业化制备神经激肽-1（NK-1）受体阻滞剂阿瑞吡坦过程中有较好的应用价值。

Abstract:

Using 4-benzyl-2-hydroxy-3-one as a starting material, a diastereoisomers of 4-b-enzyl-2-((R)-1-(3,5-bis(trifluoromethyl)phenyl)ethoxy)morpholin-3-one was prepared by two-st-ep reaction. Then the dynamic kinetic resolution of its asymmetric transformation was use-d to convert it into chiral pure (R)-4-benzyl-2-((R)-1-(3,5-bis(trifluoromethyl)phenyl)ethoxy)morpholin-3-one under potassium t-butoxide as the alkaline conditions. The ratio of the co-nverted chiral product and diastereomer is 96:4, which has greatly utility value in the pro-cess of the industrial preparation of neural excitation peptide 1 (NK-1) receptor blockers(Aprepitant).