US EPA

8721084 

Journal Article 

A new synthetic process for Tranexamic acid from ethyl 4-oxo-cyclohexane carboxylate 

Dodda, MR; Gunnam, CR; Yadharam, SR; Vanga, MR 

2016 

8 

1 

269-274 

English 

Synthesis of trans-4-aminomethylcyclohexane-1-carboxylic acid (Tranexamic acid) has been achieved by a new synthetic route starting from ethyl 4-oxocyclohexane-1-carboxylate (1) using simple and commonly available reagents and under mild conditions. The compound-1 has been converted into its cyanohydrin (2) using sodium cyanide and then, dehydrated with POCl3/Pyridine to obtain ethyl 4-cyanocyclohex-3-ene-1-carboxylate (3). It has been saponified to acid using methanolic KOH to get corresponding acid, 4-cyano-cyclohex-3-ene-1-carboxylic acid (4) which has then been subjected to reductive amination in methanolic ammonium hydroxide over the catalyst Raney nickel to obtain a mixture of 4-aminomethyl-3-cyclohexene-1-carboxylic acid (5) and its saturated analogue (6). It has been further subjected to catalytic hydrogenation over wet Pd-C (10%) in aq. methanol to obtain an isomeric mixture of 4-aminomethylcyclohexane-1-carboxylic acids (7). This, on purification by recrystallizatoin from acetone-water (4:3) has yielded pure Tranexamic acid (6). Purity of all intermediates and the title compound has been determined by GC and HPLC analyses and characterized based on their spectral and elemental analyses. Tranexamic acid obtained by this process has been of Pharma grade. Merits of the developed process are presented. 

Ethyl 4-hydroxy-4-cyanocyclohexane-1-carboxylate; Ethyl 4-oxoxyxlohexane-1-carboxylate; Haemostatic and antifibronolytic agent; Reductive amination; Saponification; Tranexamic acid