tert-Butanol → Tert-butyl (2-chloro-3-fluoropyridin-4-yl)carbamate

Participants

Reaction Conditions

Reaction Steps

To a mixture of 2-chloro-3-fluoroisonicotinic acid (3.55 g, 20.2 mmol) and triethylamine (8.4 mL, 6.13 g, 60.6 mmol) in dry toluene (40 mL) and dry t-BuOH (40 mL) under nitrogen, was added diphenylphosphoryl azide (6.51 mL, 8.27 g, 30.1 mmol). The reaction was heated at 110° C. for 3 hours then cooled to ambient temperature. The reaction mixture was concentrated under reduced pressure. The residue was dissolved in DCM (50 mL) and washed with water (40 mL). The aqueous phase was extracted with DCM (2×40 mL) and the combined organic extract was dried over MgSO4, and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (0-20% EtOAc in DCM) to give the title compound as a yellow oil (3.8 g, 71% yield). 1H NMR (400 MHz, CDCl3): δ 8.09-8.07 (m, 2H), 6.98 (br s, 1H), 1.54 (s, 9H).

Provenance & Evidence