Dimethylformamide → HCID 86694123, compound

Participants

Reaction Conditions

Reaction Steps

2-Chloro-5-fluoronicotinic acid (1.52 g, 7.36 mmol) was dissolved in a mixture of dry dimethylformamide (2 mL) and triethylamine (1.6 ml, 11.50 mmol) under nitrogen. The solution was cooled to −10° C. and diphenylphosphoryl azide (2.4 ml, 11.14 mmol) was added dropwise over 10 minutes. The reaction was stirred for 15 minutes then removed from the cold bath. After another 15 minutes the solution was diluted with ethyl acetate (200 mL) then washed with water (2×200 mL) before drying with brine (200 mL). The crude intermediate was dried further with magnesium sulfate then evaporated to dryness under reduced pressure using a 40° C. water bath. Toluene (100 mL) was added to the crude oil and the solution heated at 80° C. After 20 minutes methanol (80 mL) was added. The solution was stirred for another another 20 minutes then the mixture was evaporated to dryness under reduced pressure. The crude product was purified using silica chromatography (hexane to ethyl acetate gradient) to give the desired methyl (2-chloro-5-fluoropyridin-3-yl)carbamate (0.903 g, 4.41 mmol, 60.0% yield) as a clear oil.

Provenance & Evidence