An Improved and Practical Synthesis of Tranexamic Acid

作者：Li, Zhenhua; Fang, Li; Wang, Jian; Dong, Liuhong; Guo, Yanna; Xie, Yuanyuan^*

来源：Organic Process Research & Development, 2015, 19(3): 444-448.

DOI：10.1021/op500395b

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

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.

• 出版日期2015-3
• 单位浙江工业大学