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

Participants

Reaction Steps

A solution of tert-butyl (4-chloropyridin-2-yl)carbamate (5.5 g, 24.05 mmol) and N,N,N′,N′-tetramethylethylenediamine (7.26 mL, 48.1 mmol) in THF (100 mL) was cooled to −78° C. and treated with n-BuLi (2.5 M in hexanes, 19.24 mL, 48.1 mmol) drop wise over a period of 20 minutes. The mixture was stirred at the same temperature for 1 h. A solution of iodine (12.21 g, 48.1 mmol) in THF (40 mL) was added and stirring was continued at −78° C. for 30 min and at ambient temp of 1 h. Sat. aq NH4Cl solution (80 mL) was added and the layers were separated. The aqueous layer was extracted with EtOAc (50 mL) and the combined organics were washed with 10% aq. Na2S2O3 solution (40 mL) and brine. The extracts were dried (Na2SO4) and concentrated to dryness. A solution of 30% EtOAc-hexanes (30 mL) was added and the mixture was sonicated for 10 min. The resultant precipitate was collected by filtration, washed with 30% EtOAc-hexanes and dried in vacuo to afford tert-butyl (4-chloro-3-iodopyridin-2-yl)carbamate as off-white solid (5.6 g, 65% yield). 1H NMR (400 MHz, DMSO-d6): δ 9.45 (s, 1H); 8.28 (d, J=5.6 Hz, 1H); 7.46 (d, J=5.6 Hz, 1H); 1.43 (s, 9H).

Provenance & Evidence