Methyl 4-[(2-butyl-5-formyl-1H-imidazol-1-YL)methyl]benzoate → Eprosartan

Participants

Reaction Conditions

Reaction Steps

Methyl 4-[[2-butyl-5-formyl-1H-imidazol-1-yl]methyl]benzoate (32 gm) and ethyl 2-carboxy-3-(2-thienyl)propionate (57.15 gm) are added to cyclohexane (292 ml) under stirring at 25-30° C., the contents are heated to reflux (80-85° C.) for 2 hours under dean stark to separate the traces of water. The reaction mass is cooled to 50° C. and then slowly added a freshly prepared catalyst solution of propanoic acid (22.93 ml) in cyclohexane (53 ml) and piperidine (10.66 ml). The resulting mass is heated to reflux (80-85° C.) for 20 hours, and to the reaction mass drop wise was added a 50% NaOH solution (64 gm of NaOH in 256 ml of water) after reflux at 50° C. and then the reaction mass is heated to reflux for 2 hours. The reaction mass is cooled to 60° C., the layers separated, to the aqueous layer was added ethanol (192 ml) and then the pH of the mass is adjusted to 5.0 to 5.1 at 60° C. with 6N HCl solution (66 ml of HCl and 66 ml of water). The resulting mass was cooled to 20-25° C. and stirred for 2 hours. The mass was filtered, washed with water (100 ml) and then dried at 70-75° C. to give 26 gm of crude eprosartan free base (HPLC purity: 98.2%).

Provenance & Evidence