Sodium Bicarbonate → 5-Bromo-2-methyl-1,3-thiazole-4-carboxylic acid

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To a solution of 5-bromo-4-(dichloromethyl)-2-methyl-1,3-thiazole (7.58 g, 29.0 mmol) in ethanol (180.0 mL) was added saturated aqueous sodium bicarbonate (60.0 mL) and the system was stirred at 80° C. overnight. The mixture was then cooled to room temperature, diluted with EtOAc, extracted with water, dried over sodium sulfate and concentrated. The crude reaction mixture was purified using normal phase conditions (0%→÷30% EtOAc: hexanes) to afford a mixture of the desired compound and an acetal byproduct. This mixture was then treated with 1N HCl (12.25 mL, 12.25 mmol) for 0.5 h at room temperature followed by neutralization with 2N NaOH to a pH of 7.0. Extraction with EtOAc and water afforded the product as a pale yellow crystalline solid. To this solid (5.0 g, 24.26 mmol) in THF/t-BuOH/Water (40 mL/80 mL/20 mL) was added sodium phosphate (17.22 g, 121.0 mmol), 2-methyl-2-butene (64.0 mL, 607 mmol) and sodium chlorite (5.49 g, 60.7 mmol) and was stirred at room temperature for 1 h. The system was then acidified with 1N HCl to a pH of 3.0, extracted with EtOAc, washed with water, dried over sodium sulfate and concentrated. Removal of solvent in vacuo afforded the title compound (2-5) as a powder. 1H NMR (500 MHz, CDCl3) δ 2.72 (s, 3H). ESI+ MS: 222.8 [M+H]+.

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