Using 5-ethoxypyrimidine-2,4-diol (6.45 g) as raw material, dimethylphenylamine (5.21 ml, 1.0 eq.) and phosphorus oxychloride (POCl3, 20 ml, 5.0 eq.) were added slowly and dropwise to the slurry under ice bath conditions. The reaction mixture was then heated to reflux overnight. Upon completion of the reaction, the excess POCl3 was removed by vacuum distillation. the residue was carefully poured into ice water and filtered after complete formation of the precipitate. The resulting solid was dried under vacuum to afford the white solid product 2,4-dichloro-5-ethoxypyrimidine (2.84 g, 35.57% yield). The structure of the product was confirmed by 1H NMR (500 MHz, CDCl3): δ 1.47-1.50 (m, 3H), 4.16-4.20 (m, 2H), 8.13 (s, 1H).
