Reaktion #794424

Reaktionsgleichung

diphenylphosphoryl azide

2-Chloro-5-fluoronicotinic acid

triethylamine

dimethylformamide

→

methyl (2-chloro-5-fluoropyridin-3-yl)carbamate

Ausbeute 60.0%

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigethen removed from the cold bath
2. 2
   workup.ADDITIONAfter another 15 minutes the solution was diluted with ethyl acetate (200 mL)
3. 3
   Waschenthen washed with water (2×200 mL)
4. 4
   Trocknenbefore drying with brine (200 mL)
5. 5
   TrocknenThe crude intermediate was dried further with magnesium sulfate
6. 6
   Sonstigethen evaporated to dryness under reduced pressure
7. 7
   Sonstigeusing a 40° C.
8. 8
   workup.ADDITIONToluene (100 mL) was added to the crude oil
9. 9
   Temperaturthe solution heated at 80° C
10. 10
    workup.ADDITIONAfter 20 minutes methanol (80 mL) was added
11. 11
    workup.STIRRINGThe solution was stirred for another another 20 minutes
12. 12
    Sonstigethe mixture was evaporated to dryness under reduced pressure
13. 13
    SonstigeThe crude product was purified

Vorschrift

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.

Quelle