Example 5 Preparation of methyl 2,6-dichloro-5-methoxypyrimidine-4-carboxylate: 2,6-dichloro-5-methoxypyrimidine-4-carboxaldehyde (50 g, 0.24 mol) was dissolved in a solvent mixture of methanol (1 L) and water (60 mL). Sodium bicarbonate (400 g) was added to this solution. A methanol/water (600 mL, v/v=9:1) solution of 2M bromine (192 g, 1.2 mol) was slowly added dropwise to the pyrimidine solution over a period of 45 min at 0°C while maintaining stirring. After the dropwise addition was completed, stirring was continued at the same temperature for 1 hour. Subsequently, the reaction mixture was warmed to room temperature and stirred for 4 hours. Upon completion of the reaction, the mixture was slowly poured into a mixture containing crushed ice (2 L), sodium bisulfite (50 g) and sodium chloride (200 g). The product was extracted with ethyl acetate (1L x 2), the organic layers were combined and dried over anhydrous sodium sulfate and filtered. The solvent was removed by concentration under reduced pressure to give a viscous mass, which was left to cure to give methyl 2,6-dichloro-5-methoxypyrimidine-4-carboxylate (50.8 g, 87% yield): ESIMS m/z 238 ([M+H]+).
