Nitromethane → 1-Fluoro-2-[4-(2-nitroethyl)phenoxy]benzene

Temperatur

110 °C

To an acetic acid (30.0 mL) solution of 4-(2-fluoro-phenoxy)-benzaldehyde (3.00 g, 13.9 mmol) described in Manufacturing Example 83-1-1 were added nitromethane (4.24 g, 69.5 mmol) and ammonium acetate (2.14 g, 27.8 mmol) under nitrogen atmosphere, which was stirred for 3 hours at 110° C. Water and ethyl acetate were added to the reaction mixture, and the organic layer was extracted with ethyl acetate. The organic layer was washed with water and saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under a reduced pressure to obtain a crude product (3.60 g). To a dimethyl sulfoxide (50.0 mL) solution of this crude product (3.60 g) and acetic acid (3.00 mL) was added sodium borohydride (789 mg, 20.9 mmol) at room temperature while cooling appropriately, which was stirred for 20 minutes at room temperature. Water was then added dropwise at room temperature while cooling appropriately. The reaction mixture was extracted with ethyl acetate, and the organic layer was washed with water and saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under a reduced pressure, and the residue was purified by NH silica gel column chromatography (ethyl acetate:heptane=1:10→1:5) to obtain the title compound (1.80 g, 49.6%).

1. extractionthe organic layer was extracted with ethyl acetate
2. washThe organic layer was washed with water and saturated aqueous sodium chloride
3. dry with materialdried over anhydrous magnesium sulfate
4. filtrationfiltered
5. concentrationThe filtrate was concentrated under a reduced pressure
6. customto obtain a crude product (3.60 g)
7. temperaturewhile cooling appropriately
8. stirringwhich was stirred for 20 minutes at room temperature
9. temperaturewhile cooling appropriately
10. extractionThe reaction mixture was extracted with ethyl acetate
11. washthe organic layer was washed with water and saturated aqueous sodium chloride
12. dry with materialdried over anhydrous magnesium sulfate
13. filtrationfiltered
14. concentrationThe filtrate was concentrated under a reduced pressure
15. customthe residue was purified by NH silica gel column chromatography (ethyl acetate:heptane=1:10→1:5)

ORD-Eintrag

ord-7e7d3db3b9284e07867a87e4dc41753b

Quelldatensatz

uspto-grants-2010_04

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07691882B2