An Improved and Practical Synthesis of Tranexamic Acid

被引：16

作者：

Li, Zhenhua ^{[1
]}

Fang, Li ^{[1
]}

Wang, Jian ^{[2
]}

Dong, Liuhong ^{[2
]}

Guo, Yanna ^{[2
]}

Xie, Yuanyuan ^{[1
]}

机构：

[1] Zhejiang Univ Technol, Coll Pharmaceut Sci, Collaborat Innovat Ctr Yangtze River Delta Reg Gr, Hangzhou 310014, Zhejiang, Peoples R China

[2] Engn Res Ctr Middle High Pressure Catalyt Hydroge, Taizhou 317300, Peoples R China

来源：

ORGANIC PROCESS RESEARCH & DEVELOPMENT | 2015年 / 19卷 / 03期

基金：

中国国家自然科学基金;

关键词：

PRIMARY AMINES; CATALYZED HYDROGENATION; ANTIPLASMIN DRUGS; AROMATIC NITRILES; REDUCTION; CONVERSION; DISCOVERY; AMIDES;

D O I：

10.1021/op500395b

中图分类号：

O69 [应用化学];

学科分类号：

081704 ;

摘要：

Tranexamic acid 1, a synthetic antifibrinolytic drug with the treatment being considered highly cost-effective in many countries, has been included in the WHO list of essential medicines. In this paper, we designed the synthesis of 1 via a novel seven-step route from the readily available starting material dimethyl terephthalate, performing with 99.6% purity in 59.2% overall yield. During the process, we successfully developed a direct and efficient method for the preparation of key intermediate methyl 4-(acetamidomethyl)benzoate by one-pot hydrogenation and acylation in acetic anhydride using Ni/Al2O3 as a catalyst. More importantly, it should be a straightforward and practical way to circumvent the usage of toxic reagents (CrO3, Cl-2), solvent (CCl4), and expensive catalyst (PtO2), etc., that plagued the previous methodologies.

引用

页码：444 / 448

页数：5

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