Step 1a Synthesis of 4-chloro-5-fluoro-6-methoxy-2-methylpyrimidine: 3.21 g of sodium methanol was slowly added to 80 mL of tetrahydrofuran (THF) cooled solution containing 9.8 g of 2-methyl-4,6-dichloro-5-fluoropyrimidine, and the reaction system was maintained in an ice bath condition at a controlled temperature of 5 °C. After addition, the ice bath was removed. The reaction suspension was stirred continuously for 3 hours at room temperature. Upon completion of the reaction, the reaction mixture was again cooled to 5°C in an ice bath. Subsequently, 20 mL of water and 100 mL of ethyl acetate were added to the reaction system for extraction. After separation of the organic phase, it was dried with anhydrous magnesium sulfate, filtered, and the solvent was concentrated under reduced pressure to give 9 g of a colorless oily product, 4-chloro-5-fluoro-6-methoxy-2-methylpyrimidine. The product was purified by crystallization and characterized by the following data: mass spectrometry (Method A) showed retention time Tr (min) = 0.82; molecular ion peak [M+H]+: m/z 177.
