2-Chloro-4-methoxy-6-methylpyrimidine

7749-47-5

22536-64-7

General procedure for the synthesis of 2-chloro-4-methoxy-6-methylpyrimidine from 2-amino-4-methoxy-6-methylpyrimidine: 2-amino-4-methoxy-6-methylpyrimidine (5 g, 35.97 mmol) was dissolved in concentrated hydrochloric acid (50 ml), and aqueous (5 ml) solution of sodium nitrite (2.97 g, 43.16 mmol) was slowly added dropwise. The reaction was maintained at 0°C for 30 min followed by stirring at room temperature for 1 hr. After completion of the reaction, the reaction was quenched with 10N sodium hydroxide solution and the insoluble material was removed by filtration. The filtrate was subjected to liquid-liquid partitioning with ethyl acetate (AcOEt) and saturated saline, and the aqueous layer was then extracted with ethyl acetate. The organic layers were combined, dried with anhydrous sodium sulfate (Na2SO4), filtered and concentrated under reduced pressure to give a brown oily crude product. The crude product was purified by fast column chromatography (silica gel: 100-200 mesh, eluent: ethyl acetate-petroleum ether; 10:90→15:85) to obtain 600 mg (8% yield) of white solid, which was the target compound 2-chloro-4-methoxy-6-methylpyrimidine.