General procedure for the synthesis of ethyl 2-bromothiazole-5-carboxylate from ethyl 2-aminothiazole-5-carboxylate: to a stirred solution of ethyl 2-aminothiazole-5-carboxylate (10.0 g, 46.45 mmol, Combi block) in 48% hydrobromic acid (75 mL) at 0 °C, sodium nitrite (4.80 g, 50 mL) dissolved in water (50 mL) was added dropwise. 69.68 mmol) solution. The reaction mixture was continued to be stirred at 0 °C for 15 min. Subsequently, a 48% hydrobromic acid (75 mL) solution of copper(I) bromide (6.66 g, 46.45 mmol) was added dropwise at 0°C. The resulting reaction mixture was stirred at room temperature for 4 hours. After completion of the reaction, the reaction mixture was diluted with dichloromethane (200 mL), washed sequentially with water (50 mL) and brine (50 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure. Purification of the crude product by fast chromatography (100% chloroform) afforded ethyl 2-bromothiazole-5-carboxylate as a yellow liquid in 50% yield (5.5 g).LCMS (Method A): 235.9 (M + H), retention time 3.85 min, purity 98.6% (max).1H NMR (400 MHz, DMSO-d6): δ 8.16 (s, 1H ), 4.38 (q, J = 7.1 Hz, 2H), 1.39 (t, J = 7.1 Hz, 3H).
