Ethyl chloroacetate → 2-(4-Trifluoromethyl-phenyl)-thiazole-5-carboxylic acid ethyl ester

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Reaction Steps

To a solution of NaOEt (21% in EtOH, 215 ml, 584 mmol) were added ethyl formate (46.97 ml, 584 mmol) and then, with cooling (max. 28° C.), chloro acetic acid ethyl ester in Et2O (200 ml). The mixture was stirred at RT for 20 h and filtered after adding Et2O (200 ml). The resulting solid was dissolved in EtOH (400 ml) and after addition of 4-(trifluoromethyl)benzene-1-carbothioamide (11.98 g, 58.4 mmol) stirring to reflux was accomplished for 20 h. After filtration, the EtOH was removed under reduced pressure and extracted with CH2Cl2 (3×)/H2O. The organic phases were washed with H2O, dried (Na2SO4) and evaporated to give crude compound which was crystallized (Et2O/n-pentane) to give 12.43 g (71%) of 2-(4-trifluoromethyl-phenyl)-thiazole-5-carboxylic acid ethyl ester as off-white crystals, MS: 301 (M+), MP: 98-110° C.

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