To a 2L three-necked round-bottomed flask was added 2,4,6-tribromopyrimidine (54 g, 170.47 mmol, 1 eq.), methanol (500 mL), ethyl ether (500 mL), and a methanolic solution of sodium methanolate (30%, 76.7 g, 2.50 eq.), dropwise. The reaction mixture was stirred at room temperature for 2 hours. After completion of the reaction, the mixture was concentrated in vacuum. The concentrate was diluted with 1 L of ethyl acetate and the organic layer was subsequently washed with 3 x 500 mL of saturated sodium chloride solution. The organic layer was again concentrated in vacuum. The residue was purified by silica gel column chromatography with ethyl acetate/petroleum ether (1:100 to 1:10) as eluent. The fractions containing the target product were combined and concentrated in vacuo to afford 23 g (62% yield) of 4-bromo-2,6-dimethoxypyrimidine as a white solid. The product was confirmed by LC-MS analysis: (ES, m/z): RT = 1.287 min, LCMS 28: m/z = 219 [M + 1].
