General procedure for the synthesis of 2-chloro-4-iodopyrimidine from 2-chloropyrimidine: n-butyllithium (ca. 1.6 M hexane solution, 3.0 mmol) was sequentially added to a stirred solution of 2,2,6,6-tetramethylpiperidine (0.50 mL, 3.0 mmol) in tetrahydrofuran (THF, 6 mL) at 0 °C. After 5 min, ZnCl2-TMEDA ( 0.26 g, 1.0 mmol). The reaction mixture was continued to be stirred at 0 °C for 15 min, followed by the addition of 2-chloropyrimidine (0.11 g, 1.0 mmol). After 2 h of reaction at this temperature, a THF (10 mL) solution of iodine (I2, 0.76 g, 3.0 mmol) was added. The mixture was stirred overnight and upon completion of the reaction, the reaction was quenched by the addition of saturated sodium thiosulfate (Na2S2O3, 10 mL) solution and extracted with ethyl acetate (AcOEt, 3 x 20 mL). The organic layers were combined, dried with anhydrous magnesium sulfate (MgSO4), filtered and concentrated under reduced pressure. Purification by silica gel column chromatography (eluent: heptane/ethyl acetate, 95/5) afforded the target product 2-chloro-4-iodopyrimidine (4a) in 18% yield as a beige powder.
