Ethyl 2-chlorothiazole-5-carboxylate

32955-21-8

81449-93-6

The general procedure for the synthesis of ethyl 2-chloro-1,3-thiazole-5-carboxylate from ethyl 2-aminothiazole-5-carboxylate was as follows: ethyl 2-aminothiazole-5-carboxylate (1.0 g, 6.35 mmol) was dissolved in a solvent mixture of acetonitrile (10 mL) and tetrahydrofuran (10 mL) at 23 °C. The solution was then slowly added to a mixture of acetonitrile (10 mL) and tetrahydrofuran (10 mL) containing butyl nitrite (1.3 mL, 9.52 mmol) and cuprous chloride (1.0 g, 7.6 mmol). The reaction mixture was to be heated at 65°C until thin layer chromatography (TLC) analysis (unfolding agent was 40% ethyl acetate-hexane) showed complete consumption of the raw materials. After completion of the reaction, the mixture was cooled to room temperature and extracted by partitioning between water and ethyl acetate. The organic layer was collected, concentrated under reduced pressure and finally purified by fast silica gel column chromatography with 20% ethyl acetate-hexane as eluent to afford the target product ethyl 2-chloro-1,3-thiazole-5-carboxylate (0.49 g, 40% yield).