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

Participants

Reaction Conditions

Reaction Steps

A solution of (4-chloro-pyridin-2-yl)-carbamic acid tert-butyl ester (CB Research and Development Inc., 5.0 g, 22.0 mmol), TMEDA (8 mL) in anhydrous THF (100 mL) was placed under a nitrogen atmosphere and cooled to −70° C. and treated dropwise with 2.5 M n-BuLi in hexanes (22.0 mL, 54.8 mmol) over a period of 30 min. The mixture was stirred at −70° C. for 1 h then treated dropwise with a solution of I2 (14 g, 110 mmol) in anhydrous THF (16 mL) at −70° C. After the addition was complete, the reaction was stirred at −70° C. for 30 min then allowed to warm to room temperature. The mixture was treated with a solution of sodium hydrogensulfite (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 on SiO2 eluting with 0-5% MeOH/CH2Cl2 to give the title compound (5.8 g, 78%) as white solid. 1H NMR (DMSO-d6) δ 9.46 (s, 1H), 8.29 (d, 1H, J=5.6 Hz), 7.46 (d, 1H, J=5.0 Hz), 1.44 (s, 9H); MS(ESI−): m/z 352.99 (M−H)−.

Provenance & Evidence