Synthesis
The synthesis of methyl 2-bromothiazole-4-carboxylate is as follows:
The crude ethyl ester 228 (12.7 g) was dissolved in methanol (150 mL), and concentrated sulfuric acid (1 mL) was added. The mixture was heated to reflux for 12 hr (TLC control). The solvent was evaporated, the residue was diluted with H2O (150 mL), neutralized with saturated sodium bicarbonate solution, and extracted with dichloromethane (4 x 100 mL). The combined extracts were dried with sodium sulfate and concentrated. Purification by column chromatography (silica gel, 80 g, ethyl acetate/cyclohexane = 1:15) gave 6.5 g methyl ester 230 (29.4 mmol, 49 % over three steps) as a colorless solid. TLC: Rf = 0.55 (ethyl acetate/cyclohexane = 1:2).
