Step 2: Synthesis of 2-chloro-4-methyl-6-(trifluoromethyl)pyrimidine
To 4-methyl-6-(trifluoromethyl)pyrimidin-2(1H)-one (1 eq.) was added phosphorus oxychloride (POCl3, 5 eq.). The reaction mixture was stirred under reflux conditions overnight. Upon completion of the reaction, the mixture was cooled to room temperature and subsequently quenched with ice water and neutralized with saturated sodium hydroxide (NaOH) solution at 0 °C. After extraction with ethyl acetate (EtOAc), the organic phases were combined and dried over anhydrous sodium sulfate (Na2SO4) and subsequently concentrated under reduced pressure. The crude product was purified by column chromatography (eluent ratio: ethyl acetate:hexane = 1:4) to afford the target compound 2-chloro-4-methyl-6-(trifluoromethyl)pyrimidine.
Example 26: 2-chloro-4-methyl-6-(trifluoromethyl)pyrimidine was prepared according to the synthesis of Example 25, using 4-methyl-6-(trifluoromethyl)pyrimidin-2-ol as starting material, to obtain 2-chloro-4-methyl-6-(trifluoromethyl)pyrimidine as a brown oily material in 37% yield. The compound showed no ionization signal in LC-MS analysis.1H NMR (CDCl3) data were as follows: δ 7.44 (s, 1H), 2.68 (s, 3H).
