The general procedure for the synthesis of ethyl 2-(4-bromophenyl)-thiazole-4-carboxylate from ethyl 3-bromopyruvate and 4-bromothiobenzamide is as follows:
(i) Ethyl 3-bromopyruvate (0.18 mL, 1.0 mmol) was slowly added to an ethanol solution (3 mL) of 4-bromothiobenzamide (529 mg, 1.0 mmol).
(ii) The reaction mixture was stirred at room temperature for 6 h. The precipitated crystals were subsequently collected by filtration and dried.
(iii) The dried crystals were slowly added dropwise to concentrated sulfuric acid (5 mL) and stirred at room temperature for 3 hours.
(iv) The solvent was removed by distillation and the residue was diluted with ethyl acetate.
(v) The diluted solution was washed sequentially with saturated aqueous sodium bicarbonate and deionized water, and the organic layer was dried with anhydrous magnesium sulfate.
(vi) After filtration, the filtrate was concentrated and the resulting crystals were collected by filtration and dried to afford ethyl 2-(4-bromophenyl)-thiazole-4-carboxylate (285 mg, 91% yield).
Product characterization data:
1H-NMR (300 MHz, CDCl3) δ: 1.30 (3H, t, J = 7.5 Hz), 4.30 (1H, q, J = 7.5 Hz), 7.65 (2H, d, J = 7.8 Hz), 7.85 (2H, d, J = 7.8 Hz), 8.15 (1H, s).
MS (FAB) m/z: 313 (M+ +1).
