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5.2 Synthesis of 2-methyl-5-ethoxycarbonyl-4-hydroxythiazole: Diethyl 2-bromomalonate (168 g, 0.7 mol) was slowly added to a 400 mL solution of toluene containing thioacetamide (52.5 g, 0.7 mol). The reaction mixture was heated to reflux for 1 hour. Upon completion of the reaction, the mixture was cooled to room temperature and filtered through a diatomaceous earth pad. Subsequently, the toluene was evaporated under reduced pressure to give a viscous oily crude product. This crude product was mixed with 500 mL of water and stirred until solids precipitated. The solid product was collected by filtration, washed sequentially with water (3 x 300 mL) and petroleum ether, and finally dried under high vacuum to afford 55 g of methyl 4-hydroxy-2-methylthiazole-5-carboxylate (yield: 42%; LC retention time: 1.24 min; MS: [M+H]+ = 188).