Efficient and scalable process for the synthesis of antihypercholesterolemic drug ezetimibe

被引：13

作者：

Zhu, Yijun ^{[1
,2
]}

Pan, Jing ^{[1
]}

Zhang, Shunli ^{[1
]}

Liu, Zhenren ^{[1
]}

Ye, Deyong ^{[2
]}

Zhou, Weicheng ^{[1
]}

机构：

[1] State Inst Pharmaceut Ind, Shanghai Key Lab Antiinfect, State Key Lab New Drug & Pharmaceut Proc, Shanghai, Peoples R China

[2] Fudan Univ, Sch Pharm, Shanghai, Peoples R China

来源：

SYNTHETIC COMMUNICATIONS | 2016年 / 46卷 / 20期

关键词：

(S)-4-phenyl-2-oxazolidinone; ezetimibe; NaBH4/I-2; process; stereoselective; CHOLESTEROL ABSORPTION INHIBITORS; PRIMARY HYPERCHOLESTEROLEMIA; ENANTIOSELECTIVE REDUCTION; KETONES; NABH4/I-2;

D O I：

10.1080/00397911.2016.1221969

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

An efficient and scalable process for the synthesis of antihypercholesterolemic drug ezetimibe through chiral Evans auxiliary (S)-4-phenyl-2-oxazolidinone is described. The key steps in this process are the condensation of (S)-3-(5-(4-fluorophenyl)-5,5-dimethoxypentanoyl)-4-phenyloxazolidin-2-one and N-(4-((tert-butyldimethylsilyl)oxy)benzylidene)-4-fluoroaniline, and the stereoselective reduction of ezetimibe-ketone with NaBH4/I-2, which is first applied in the synthesis of ezetimibe. The process is concise, mild, easy to operate, and highly stereoselective (99.6% of de value of ezetimibe). In addition, three diastereomers of ezetimibe are synthesized and served as the references in quality control of the product. [GRAPHICS] .

引用

页码：1687 / 1693

页数：7

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