1192813-64-1

1895-39-2

4983-28-2

1192813-64-1

Step A: Synthesis of 2-chloro-5-(difluoromethoxy)pyrimidine 2-Chloropyrimidin-5-ol (1 g, 7.66 mmol) and sodium 2-chloro-2,2-difluoroacetate (3.50 g, 22.98 mmol) were dissolved in N,N-dimethylformamide (20 mL), water (0.2 mL) was added, and the reaction mixture was heated to 90 °C for 24 hours. After completion of the reaction, the solvent was removed by vacuum concentration. The crude product was purified by column chromatography (eluent: 5-30% ethyl acetate/hexane) to afford 2-chloro-5-(difluoromethoxy)pyrimidine (549 mg, 3.04 mmol, 39.7% yield) as a light yellow oil. Mass spectrometry (LC/MS) analysis showed retention time (R.T.) = 1.32 min; [M+H]+ = 181.14.