General procedure for the synthesis of methyl 5-bromo-4-thiazolecarboxylate from methyl 2-amino-5-bromothiazole-4-carboxylate: Methyl 2-amino-5-bromothiazole-4-carboxylate (1.0 equiv, 100 mg, 0.42 mmol) was dissolved in anhydrous DMF (0.8 mL). The reaction mixture was heated to 80 °C under nitrogen protection. A solution of tert-butyl nitrite (1.2 eq, 60 μL, 0.50 mmol) in DMF (0.8 mL) was slowly added dropwise to the hot solution. After several minutes of reaction, no gas escaped indicating completion of the reaction. The reaction mixture was cooled to room temperature and then sampled directly onto a preloaded silica gel column. Rapid column chromatographic separation was carried out sequentially using hexane and ethyl acetate/hexane (2:8, v/v) as eluents to afford methyl 5-bromothiazole-4-carboxylate as a yellow solid (49 mg, 53% yield). The product was analyzed by LCMS (ES) showing a purity of 95%, m/z 222 [M]+, 224 [M+2]+.
