Synthesis
To a solution of 2,4-dibromothiazole (50 g, 207 mmol, 1.0 eq.) in anhydrous ether (1000 ml) was slowly added n-butyllithium (90 ml, 2.5 M, 1.1 eq.) dropwise at -78 °C. The temperature was maintained at -78 °C and the reaction mixture was stirred for 1 hour. Subsequently, the reaction solution was poured into dry carbon dioxide at the same temperature and the reaction mixture was gradually warmed up to room temperature. The completion of the reaction was confirmed by monitoring the progress of the reaction by thin layer chromatography (TLC) and liquid chromatography-mass spectrometry (LCMS). After completion of the reaction, the reaction was quenched with deionized water (100 ml). The ether phase was separated and discarded. The aqueous phase was adjusted to pH 2-3 with dilute hydrochloric acid and then extracted with ethyl acetate. The organic phases were combined, dried with anhydrous sodium sulfate, filtered and concentrated under reduced pressure to give 35 g of 4-bromo-1,3-thiazole-2-carboxylic acid in 82% yield. The product was characterized by 1H NMR (400 MHz, DMSO-d6): δ 8.23 (1H, s).
References
[1] Patent: US2014/179663, 2014, A1. Location in patent: Paragraph 0174
[2] Journal of Fluorine Chemistry, 1991, vol. 55, # 2, p. 173 - 178
[3] Patent: WO2008/57336, 2008, A2. Location in patent: Page/Page column 36
[4] Patent: US2015/175597, 2015, A1. Location in patent: Paragraph 0179; 0180
