An improved and practical synthesis of tranexamic acid

Article abstract of DOI:10.1021/op500395b

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, Cl₂), solvent (CCl₄), and expensive catalyst (PtO₂), etc., that plagued the previous methodologies.