Sodium Carbonate → Di-tert-butyl(2-chloro-6-phenylpyridin-3-yl)imidodicarbonate

Participants

Reaction Conditions

Reaction Steps

2,6-dichloropyridin-3-amine (9.39 g, 57.6 mmol), di-tert-butyldicarbonate (503 g, 230 mmol), DMAP (0.704 g, 5.76 mmol) and triethylamine (16.06 mL, 115 mmol) were combined in DCM (230 mL) and stirred at RT overnight. The solvent was evaporated and the residue was triturated with acetonitrile and filtered to provide di-tert-butyl(2,6-dichloropyridin-3-yl)imidodicarbonate. Di-tert-butyl(2,6-dichloropyridin-3-yl)imidodicarbonate (27.7 g, 76 mmol), phenyl boronic acid (13.95, 114 mmol) and sodium carbonate (114 mL, 229 mmol, 2M) were combined with dioxane (692 ml) and DMF (46 ml). The solution was purged with N2 for 20 min. Tetrakis(triphenylphosphine)palladium(0) (4.41 g, 3.81 mmol) was added and reaction heated to 85° C. for 3 h, then cooled to RT and stirred overnight. Reaction was poured into H2O (100 ml) and extracted with EtOAc (2×100) ml. The combined organics were washed with brine and dried over Na2SO4. Crude product was purified by flash chromatography on ISCO 330 g column. (0-20% EtOAc/Heptane). Major spot (TLC 10:1 Heptane/EtOAc) isolated to give 12.06 g of di-tert-butyl(2-chloro-6-phenylpyridin-3-yl)imidodicarbonate as a white solid. 1H NMR (CDCl3) δ 8.01 (d, J=7.0 Hz, 2H), 7.69 (d, J=8.1 Hz, 1H), 7.58 (d, J=8.1 Hz, 1H), 7.41-7.48 (m, 3H), 1.40 (s, 18H); MS: cal'd 405 (MH+), exp 405 (MH+).

Provenance & Evidence