Synthesis
General procedure for the synthesis of 2-bromo-4-methylthiazole-5-carboxylic acid from ethyl 2-bromo-4-methyl-1,3-thiazole-5-carboxylate: 5N aqueous NaOH solution (15 mL) was added to a solution of ethyl 2-bromo-4-methyl-1,3-thiazole-5-carboxylate (1 mmol) in ethanol (20 mL), and the reaction mixture was stirred for 14 h at room temperature. The reaction progress was monitored by thin layer chromatography (TLC). After completion of the reaction, the mixture was cooled and neutralized with concentrated hydrochloric acid. The organic layer was extracted with ethyl acetate (EtOAc) and the organic phase was dried with anhydrous sodium sulfate (Na2SO4). The solvent was removed by concentration under reduced pressure to give the crude product. The crude product was purified by column chromatography using silica gel (60-120 mesh) as stationary phase and gradient elution with a mixed solvent of ethyl acetate and petroleum ether, which ultimately afforded 2-bromo-4-methylthiazole-5-carboxylic acid as an off-white solid in 76% yield. The structure of the product was confirmed by 1H NMR (CDCl3, δ: 13.19, s, 1H; 2.54, s, 3H) and mass spectrometry (ESI-MS, m/z: 223 [M+H]+).
References
[1] Patent: EP2604268, 2015, B1. Location in patent: Paragraph 0150-0151
[2] Russian Journal of General Chemistry, 2016, vol. 86, # 7, p. 1722 - 1729
[3] Zh. Obshch. Khim., 2016, vol. 86, # 7, p. 1722 - 1729,8
[4] Justus Liebigs Annalen der Chemie, 1890, vol. 259, p. 298
[5] Roczniki Chemii, 1972, vol. 46, p. 1647 - 1658
