Synthesis
General procedure for the synthesis of 4-chloro-5-fluoro-2-methylpyrimidine from 5-fluoro-2-methylpyrimidin-4(3H)-one: 5-fluoro-2-methylpyrimidin-4(3H)-one (1.04 g, 7.21 mmol) and N,N-dimethylaniline (1.80 mL) were dissolved in phosphorus trichloride and heated to a reaction temperature of 110 °C for 90 min. After the reaction was completed, it was cooled to room temperature and the reaction mixture was carefully poured into ice water. The product was extracted with diethyl ether, and the ether layer was washed sequentially with 2N hydrochloric acid, water and saturated saline, and then dried with anhydrous magnesium sulfate. The ether was removed by careful evaporation under reduced pressure to give the volatile liquid product 4-chloro-5-fluoro-2-methylpyrimidine (0.39 g, 34% yield), which could be used in subsequent reactions without further purification. Thin layer chromatography (TLC) Rf value was 0.26 (unfolding agent: 10% ethyl acetate/hexane).1H NMR (400 MHz, DMSO-d6): δ 3.91 (s, 3H), 8.79 (s, 1H).
