tert-Butanol → 3-N-Boc-aMino-2-chloro-5-fluoropyridine

Participants

Reaction Conditions

Reaction Steps

2-Chloro-5-fluoronicotinic acid (7.03 g, 40.0 mmol) was dissolved in a mixture of toluene (100 mL), tert-butanol (20 ml, 209 mmol), and triethylamine (6.8 ml, 48.9 mmol). Diphenylphosphoryl azide (9 ml, 41.8 mmol) was added slowly and the reaction heated at 90° C. After 2 hours the reaction was cooled and concentrated under reduced pressure. The residue was partitioned between water (100 mL), saturated sodium bicarbonate (70 mL) and ethyl acetate (300 mL). The organic was dried with magnesium sulfate and evaporated to dryness under reduced pressure. Purification using silica chromatography (hexane to ethyl acetate gradient) gave the desired tert-butyl (2-chloro-5-fluoropyridin-3-yl)carbamate (4.97 g, 20.15 mmol, 50.3% yield) as a thick oil.

Provenance & Evidence