General procedure for the synthesis of ethyl 2-trifluoromethyl-4-chloropyrimidine-5-carboxylate using ethyl 4-hydroxy-2-trifluoromethylpyrimidine-5-carboxylate as starting material:
1. ethyl 4-hydroxy-2-trifluoromethylpyrimidine-5-carboxylate (51.8 g) was dissolved in dichloromethane (600 mL) under ice bath conditions.
2. Oxalyl chloride (57.4 mL) was slowly added to the above solution, followed by dimethylformamide (0.2 mL) as a catalyst.
3. The reaction mixture was stirred at room temperature for 16 hours.
4. Upon completion of the reaction, the solvent was removed by rotary evaporator.
5. Toluene was added and evaporated again to completely remove residual oxalyl chloride and by-products.
6. The residue is redissolved in methylene chloride and the organic layer is washed with water to remove water-soluble impurities.
7. The organic layer was dried using anhydrous magnesium sulfate, filtered and concentrated by rotary evaporator to afford the title compound ethyl 2-trifluoromethyl-4-chloropyrimidine-5-carboxylate as an orange oil (55.7 g, 100% yield).
Product characterization data:
1H-NMR (CDCl3) δ 9.25 (1H, s), 4.51 (2H, q), 1.46 (3H, t);
13C-NMR (CDCl3) δ 126.0 (2C), 161.1, 158.1 (q, J = 39 Hz), 127.0, 118.9 (q, J = 276 Hz), 63.5, 14.4.
