Iodine → tert-Butyl (6-chloro-4-iodopyridin-3-yl)carbamate

Participants

Reaction Steps

To a solution of TMEDA (25.4 g, 219.3 mmol) in dry THF (300 mL) was added dropwise n-BuLi (87.7 mL, 219.3 mmol) at −78° C., the mixture was stirred for 0.5 h at this temperature. A solution of tert-butyl 6-chloropyridin-3-yl-carbamate (20 g, 87.7 mmol) in THF (170 mL) was added dropwise to the reaction mixture at −78° C. and the resulting mixture was continued to stir for 1 h at −78° C. Then a solution of I2 (26.7 g, 105.3 mmol) in dry THF (170 mL) was added dropwise at −78° C. After 1 h, the reaction was quenched with sat. aqueous NH4Cl (300 mL). The organic layer was separated and the aqueous phase was extracted with EtOAc (150 mL×3). The combined organic layers were dried over anhydrous Na2SO4 and concentrated under reduced pressure to yield a residue that was purified by column chromatography on silica gel (petroleum ether/ethyl acetate, 10/1) to give tert-butyl 6-chloro-4-iodopyridin-3-ylcarbamate (10.0 g, 33%). 1H-NMR (CDCl3, 400 MHz) δ 8.95 (s, 1H), 7.73 (s, 1H), 6.64 (br s, 1H), 1.53 (s, 9H).

Provenance & Evidence