General procedure for the synthesis of 5-chloro-2-iodopyridine from 2-bromo-5-chloropyridine:
1. Preparation: acetyl chloride (11.05 mL, 0.155 mol) was slowly added to a solution of 2-bromo-5-chloropyridine (20.0 g, 0.103 mol) in acetonitrile (120 mL) followed by sodium iodide (23.3 g, 0.155 mol). The reaction mixture was heated to reflux and a drying tube was fitted for 3 hours.
2. Post-treatment: after completion of the reaction, the mixture was cooled in an ice bath and saturated aqueous potassium carbonate solution was slowly added to alkalize the reaction solution. The reaction mixture was extracted with ethyl acetate (2 x 100 mL). The organic layers were combined, washed with saturated aqueous sodium sulfite (200 mL), dried over anhydrous magnesium sulfate and subsequently concentrated under reduced pressure.
3. Repeat the reaction: to ensure that the reaction was complete, the residue was subjected to the same reaction and post-treatment steps again. The target compound 5-chloro-2-iodopyridine (18.71 g, 75% yield) was finally obtained as a brown solid.
4. Characterization: 1H NMR (CDCl3, 400 MHz) δ 7.30 (1H, dd), 7.65 (1H, d), 8.35 (1H, d); LRMS (APCI+) m/z 240 [MH+].
