850832-54-1

General procedure for the synthesis of 4-bromo-5-methylisoxazole-3-carboxylic acid methyl ester from 5-methylisoxazole-3-carboxylic acid: bromine (49.4 g, 309 mmol) was slowly added dropwise to a solution of 5-methylisoxazole-3-carboxylic acid methyl ester (30 g, 206 mmol) dissolved in chloroform (103 mL) at room temperature. The reaction mixture was heated to reflux for 3 hours. After completion of the reaction, it was cooled to room temperature and the reaction mixture was poured into a mixture of saturated aqueous potassium carbonate solution and saturated aqueous sodium thiosulfate solution. It was extracted twice with chloroform and the organic layers were combined. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure to remove the solvent. The residue was purified by silica gel column chromatography with the eluent being petroleum ether: ethyl acetate (10:1, v/v) to afford methyl 4-bromo-5-methylisoxazole-3-carboxylate (27.3 g, 60% yield) as a white solid. Mass spectrometry (MS) data: 220/222 [M + H]+, APCI (methanol).

[1] Patent: WO2005/37271, 2005, A2. Location in patent: Page/Page column 185
[2] Journal of Medicinal Chemistry, 2018, vol. 61, # 18, p. 8337 - 8352