Di-tert-butyl dicarbonate → Tert-butyl (6-bromopyridin-2-YL)carbamate

Participants

Reaction Conditions

Reaction Steps

To a solution of 6-bromopyridin-2-amine (15 g, 86.49 mmol, 1 eq.) in 250 ml of DCM cooled to 0° C. were added DMAP (1.05 g, 8.67 mmol, 0.1 eq.), TEA (9.65 g, 95.36 mmol, 1.1 eq.) and BOC2O (22.70 g, 104.03 mmol, 1.2 eq.) portionwise. The reaction was stirred at 0° C. for 5 h and quenched with sat. aqueous NH4Cl. The aqueous layer was extracted with DCM, and the organics were combined, dried over MgSO4 and concentrated. The crude residue was purified by chromatography on silica gel to give impure tert-butyl (6-bromopyridin-2-yl)carbamate (mix 80/20 of mono and bis BOC) as a white solid. A chemical purification was then done. This solid was dissolved in 250 ml of THF cooled to 0° C. then iPrMgCl.LiCl (2 M, 51.89 ml, 103.78 mmol, 1.2 eq.) was added dropwise. The solution was stirred 30 min and quenched with aqueous sat. NH4Cl. The aqueous layer was separated and extracted with DCM. The organics were combined, dried over MgSO4 and concentrated to give tert-butyl (6-bromopyridin-2-yl)carbamate (15.96 g, 68%) as a white solid.

Provenance & Evidence