Facile Synthesis of Thalidomide

We report a simple and facile procedure for the preparation of thalidomide in two steps with a high overall yield (56%). The preparation was composed of a reaction between anhydride phthalic and l-glutamic acid to form N-phthaloyl-dl-glutamic acid (IV), and a cyclization step using IV reacted with ammonium acetate in diphenyl ether to create thalidomide. Reaction parameters reaction time, temperature, solvent, and molar ratio of reagents in the procedure are optimized so that the reaction performance is highest while ensuring environmental friendliness. Moreover, this process has great potential for the industrial scale of thalidomide. These compounds were identified through IR, MS, 1H NMR, and 13C NMR.