Dimethylformamide → HCID 86694123, compound

Temperature

-10 °C

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.

1. customthen removed from the cold bath
2. additionAfter another 15 minutes the solution was diluted with ethyl acetate (200 mL)
3. washthen washed with water (2×200 mL)
4. dry with materialbefore drying with brine (200 mL)
5. dry with materialThe crude intermediate was dried further with magnesium sulfate
6. customthen evaporated to dryness under reduced pressure
7. customusing a 40° C.
8. additionToluene (100 mL) was added to the crude oil
9. temperaturethe solution heated at 80° C
10. additionAfter 20 minutes methanol (80 mL) was added
11. stirringThe solution was stirred for another another 20 minutes
12. customthe mixture was evaporated to dryness under reduced pressure
13. customThe crude product was purified

ORD record

ord-dbdd5f2141a54a34b412b4a524d1409d

Source dataset

uspto-grants-2015_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09174992B2