2,5-dichloro-4-methoxypyrimidine

Sodium methoxide (295 mg, 5.45 mmol) was taken up in methanol (13.6 ml) and 2, 4, 5- trichloropyrimidine (500 mg, 2.73 mmol) was added. The mixture was stirred at roomtemperature overnight. The resulting mixture was concentrated under reduced pressure. The resulting residue was diluted with diethyl ether, washed with 1 : 1 water : saturated aqueous ammonium choride. The organic layer was dried over magnesium sulfate, filtered, and concentrated under reduced pressure. Purification by Combiflash (0-10percent diethyl ether/hexanes) afforded 280 mg (1.56 mmol, 57percent) of 2, 5-dichloro-4-methoxypyrimidine as a white solid.To a 250 mL round bottom flask equipped with a stir bar was added 1 g 5- chloro-2, 4-dichloro- pyrimidine, and 15mL of diethyl ether. The mixture was cooled to 0°C in an ice bath and then 1 equivalent of sodium methoxide in methanol (prepared from reacting 120 mg of sodium with 4 mL of methanol at room temperature) was slowly added. The reaction was stirred over night at room temperature and checked by LCMS. The white precipitate was filtered and the solid washed with cold methanol. After drying, 0.98 g of pure 2, 5-dichloro-4- methoxypyrimidine was obtained and this material was used without further purification.To a 250 mL round bottom flask equipped with a stir bar was added 1 g 5-chloro- 2, 4-dichloro- pyrimidine, and l5mL of diethyl ether. The mixture was cooled to 0°C inan ice bath and then 1 equivalent of sodium methoxide in methanol (prepared from reacting 120 mg of sodium with 4 mL of methanol at room temperature) was slowly added. The reaction was stirred over night at room temperature and checked by LCMS. The white precipitate was filtered and the solid washed with cold methanol. After drying, 0.98 g of pure 2, 5-dichloro-4-methoxypyrimidine was obtained and this material wasused without further purification.