2-Chloro-4-methoxypyrimidine is prepared by the reaction of 2,4-Dichloropyrimidine and Sodium Methoxide. The specific synthesis steps are as follows:
To a solution of 2,4-dichloropyrimidine (41.8 g, 280 mmol) in methanol (900 mL)was added a solution of CH3ONa (15.2 g, 280 mmol) in 100 mL methanol at 0 °C. The mixturewas stirred at rt for overnight. The mixture was concentrated under reduce pressure to give awhite solid, which was diluted with water (400mL) and extracted with ethyl acetate (500 mL x3). The combined organic layer was washed with brine, dried, concentrated to give 2-chloro-4-methoxypyrimidine (40 g, yield: 98percent) as white solid. ESI-MS (M+H): 145.0. ‘H NMR (400 MHz, CDC13) (5: 8.30 (d, J= 5.6 Hz ,1H), 6.68 (s, J= 5.6 Hz ,1H), 4.02 (s, 3H).