General procedure for the synthesis of tert-butyl (4-iodopyridin-3-yl)carbamate from N-tert-butoxycarbonyl-3-aminopyridine: A dry 4-necked flask was heated under argon protection and a solution of tert-butyl pyridin-3-yl-carbamate (10 g, 51.5 mmol, CAS RN 56700-70-0) in tetrahydrofuran (THF, 100 mL) was added. The reaction system was cooled to -75 °C, followed by slow dropwise addition of tert-butyllithium (1.7 M n-pentane solution, 66.6 mL, 113 mmol) over 15 min, ensuring that the reaction temperature was maintained below -60 °C. The resulting light brown suspension was stirred continuously at -75 °C for 3.75 hours. Next, a solution of iodine (28.7 g, 113 mmol) in THF (50 mL) was added dropwise over 20 min, keeping the temperature below -63 °C. The reaction mixture was continued to be stirred at -75 °C for 1.5 h before being poured into a mixture of saturated aqueous ammonium chloride (NH4Cl, 1000 mL) and ethyl acetate (EtOAc, 500 mL). The organic layer was separated, washed sequentially with 10% sodium thiosulfate (Na2S2O3, 300 mL) aqueous solution and brine (250 mL), dried over magnesium sulfate (MgSO4) and filtered. The filtrate was treated with silica gel and concentrated by evaporation. Purification was carried out using a medium pressure liquid chromatography (MPLC) system on a 120 g silica gel column by gradient elution of n-heptane: ethyl acetate (100:0 to 0:100) to give a yellow solid product (11.7 g, 71% yield). Mass spectrum (ESI): m/z = 321.1 [M + H]+.
