Phenyl imidazole propionate derivative which shows wide range of biological activities was synthesized. The yield of imidazole ring formation i.e. conversion of 1-isopropyl 3-(2-oxo-2-phenylethyl)2-(4-methoxybenzyl)malonate (1) to tert-butyl 3-(4-methoxyphenyl)-2-(4-phenyl-1H-imidazole- 2-yl)propanoate (2) was improved from 35% to 87%. Statistical model based screening and optimization DOE study were carried out to derive the most favorable design space and optimal operating condition for the process parameters. The model of optimization study was created using central composite design. Model-validation was performed which showed excellent reproducibility with high degree of precession. Use of ammonium chloride as a catalyst to improve the yield of imidazole ring formation reaction was also explored for the first time.