400777-00-6

171178-45-3

400777-00-6

Step b: Synthesis of tert-butyl 6-chloro-4-iodopyridin-3-ylcarbamate To a solution of anhydrous tetrahydrofuran (THF, 300 mL) containing tetramethylethylenediamine (TMEDA, 25.4 g, 219.3 mmol) was added n-butyllithium (n-BuLi, 87.7 mL, 219.3 mmol) slowly and dropwise at -78 °C under nitrogen protection. After the dropwise addition, the reaction mixture was stirred at -78 °C for 30 min. Subsequently, a solution of tert-butyl 6-chloropyridin-3-ylcarbamate (20 g, 87.7 mmol) in anhydrous THF (170 mL) was slowly added dropwise to the reaction system at the same temperature. After completion of the dropwise addition, the reaction mixture was continued to be stirred at -78 °C for 1 hour. Next, a solution of iodine (I2, 26.7 g, 105.3 mmol) in anhydrous THF (170 mL) was added slowly dropwise at -78 °C. After the dropwise addition was completed, the reaction mixture was continued to be stirred at -78 °C for 1 hour. Upon completion of the reaction, the reaction was quenched with saturated aqueous sodium bicarbonate (NaHCO3) and aqueous ammonium chloride (NH4Cl) (300 mL). The organic layer was separated and the aqueous phase was extracted with ethyl acetate (EtOAc, 150 mL x 3). All organic layers were combined, dried with anhydrous sodium sulfate (Na2SO4) and concentrated under reduced pressure to obtain the crude product. The crude product was purified by silica gel column chromatography (eluent: petroleum ether/ethyl acetate, 10/1) to afford the target compound tert-butyl 6-chloro-4-iodopyridin-3-ylcarbamate (10.0 g, 33% yield). Product characterization: 1H-NMR (CDCl3, 400 MHz) δ 8.95 (s, 1H), 7.73 (s, 1H), 6.64 (br s, 1H), 1.53 (s, 9H).