Iodine → 2-Boc-Amino-3-iodo-4-chloropyridine

Participants

Reaction Conditions

Reaction Steps

To a 250 mL round bottom flask was charged with tert-butyl (4-chloropyridin-2-yl)carbamate (5 g, 21.87 mmol) and dissolved in THF (109 mL). The stirring solution was placed in a dry ice bath and cooled to −78° C. TMEDA (8.25 mL, 54.7 mmol) was then added and the flask was flushed with nitrogen. 2.5M n-BuLi in hexanes (21.87 mL, 54.7 mmol) was then added over a period of 30 min. The mixture was stirred at −78° C. for 1 h then treated drop wise with a solution of iodine (13.87 g, 54.7 mmol) in anhydrous THF (16 mL) at −78° C. After the addition was complete, the reaction was stirred at −78° C. for 30 min then allowed to warm to rt. The mixture was treated with a solution of sodium hydrogen sulfite (16 g) in H2O (100 mL) and stirred for 30 min then extracted with EtOAc. The extract was washed with brine, dried (MgSO4) and concentrated in vacuo. The product was purified by flash chromatography: (90 g, equilibrated with DCM, loaded with DCM, initial waste: 0 mL, fraction size: 27 mL 18×150 mm, and eluted with MeOH in dichloromethane 0% [180 mL], 0-5% [360 mL], 5% [700 mL]). Collected fractions to give tert-butyl (4-chloro-3-iodopyridin-2-yl)carbamate (6.59 g, 85% yield) as a yellow solid. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 8.28 (d, J=5.0 Hz, 1H), 7.43 (br. s., 1H), 7.10 (d, J=5.0 Hz, 1H), 1.56 (s, 9H)

Provenance & Evidence