2-Chloro-4-methylpyrimidine

5424-21-5

13036-57-2

Step A: Synthesis of 2-chloro-4-methylpyrimidine To a vigorously stirred slurry containing 50.0 g (0.31 mol) of 2,6-dichloro-4-methylpyrimidine, 250 mL of ethanol (EtOH), and 250 mL of water, 41 g (0.63 mol) of zinc powder and 0.78 g (3.08 mmol) of iodine were sequentially added. The reaction mixture was heated to reflux at 70°C for 4 hours. After completion of the reaction, the mixture was cooled to room temperature and filtered. The filtrate was concentrated under reduced pressure to remove ethanol and subsequently extracted with dichloromethane (DCM). The organic layers were combined, dried with anhydrous magnesium sulfate (MgSO4), filtered and concentrated under reduced pressure to remove solvent. The residue was purified by silica gel column chromatography using a hexane/DCM solvent mixture as eluent, resulting in 20.6 g (53% yield) of 2-chloro-4-methylpyrimidine as a white solid. The structure of the product was confirmed by 1H-NMR (d6-DMSO, 400 MHz) δ 8.59 (d, 1H, J=4.9 Hz), 7.44 (d, 1H, J=4.9 Hz), and 3.29 (s, 3H), and ESIMS: 129.11 (M+H+).