Water → HCID 61720969, compound

Temperature

100 °C

A mixture of 2-bromo-1-(2,4-difluorophenoxy)-4-nitrobenzene (22.5 g, 68.2 mmol), iron powder (19.04 g, 341 mmol), and ammonium chloride (7.30 g, 136 mmol) in tetrahydrofuran (117 mL), ethanol (117 mL), and water (39.0 mL) was heated under reflux at 100° C. for 2 hours. The reaction mixture was cooled to just below reflux temperature, filtered through Celite, and the filter cake washed with warm methanol (3×50 mL). The resulting solution was concentrated under reduced pressure and then neutralized to a pH of 8 with saturated sodium hydrogen carbonate (150 mL). The mixture was extracted with ethyl acetate (3×100 mL). The combined organics were washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, filtered, and concentrated. The residue was purified by flash chromatography (silica gel, ethyl acetate/hexane gradient 0-15%) to provide 3-bromo-4-(2,4-difluorophenoxy)aniline (16.8 g, 82% yield).

1. temperaturewas heated
2. temperatureThe reaction mixture was cooled to just
3. temperaturebelow reflux temperature
4. filtrationfiltered through Celite
5. washthe filter cake washed with warm methanol (3×50 mL)
6. concentrationThe resulting solution was concentrated under reduced pressure
7. extractionThe mixture was extracted with ethyl acetate (3×100 mL)
8. washThe combined organics were washed with saturated aqueous sodium chloride
9. dry with materialdried over anhydrous magnesium sulfate
10. filtrationfiltered
11. concentrationconcentrated
12. customThe residue was purified by flash chromatography (silica gel, ethyl acetate/hexane gradient 0-15%)

ORD record

ord-eb7f6f01ae344ef5b9131436c20d2d3b

Source dataset

uspto-grants-2016_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09321765B2