4-Bromo-2,6-difluoroaniline → 5-Bromo-1,3-difluoro-2-nitrobenzene

Temperatur

65 °C

To a suspension of sodium perborate tetrahydrate (1.78 mmol, 0.27 g) in 10 ml of acetic acid stirred at 65° C. was added a solution of (4-bromo-2,6-difluorophenyl)amine (1.78 mmol, 0.42 g, 1 eq.) in 5 ml of acetic acid over one hour dropwise. The reaction was heated at 65° C. over 3 days. Sodium perborate tetrahydrate (2 eq., 3.56 mmol, 0.54 g) was added again. After 3 hours, sodium perborate tetrahydrate (1 eq., 1.78 mmol, 0.27 g) was added again. Additional sodium perborate tetrahydrate (3 eq., 5.34 mmol, 0.81 g) was again added. The reaction was then left overnight at 70° C. under reflux and under argon. The solution was then cooled to room temperature and poured onto ice and extracted with ethyl acetate (2×). The combined organics were washed with water and brine. The organics were dried over MgSO4, filtered and the organic solvent was removed under reduced pressure to afford the crude product which was purified by silica chromatography (ethyl acetate-4% n-hexane 96%) to afford the title compound, 0.29 g, 68%.

1. temperatureThe reaction was heated at 65° C. over 3 days
2. waitThe reaction was then left overnight at 70° C.
3. temperatureunder reflux and under argon
4. temperatureThe solution was then cooled to room temperature
5. additionpoured onto ice
6. extractionextracted with ethyl acetate (2×)
7. washThe combined organics were washed with water and brine
8. dry with materialThe organics were dried over MgSO4
9. filtrationfiltered
10. customthe organic solvent was removed under reduced pressure
11. customto afford the crude product which
12. customwas purified by silica chromatography (ethyl acetate-4% n-hexane 96%)

ORD-Eintrag

ord-946d62b7c6954c9d83b9f85c44c5ef13

Quelldatensatz

uspto-grants-2013_07

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08481566B2