Carbon Tetrachloride → 3-Fluoro-4-nitrobenzaldehyde

In a round bottom flask under nitrogen was combined 3-Fluoro-4-nitrotoluene (15 g, 96.7 mMol), N-bromosuccinimide (37.9 g, 212.7 mMol), and carbon tetrachloride (300 mL). The mixture was stirred at room temperature and benzoyl peroxide added (2.34 g, 9.67 mMol). A water-cooled reflux condenser was attached and the solution heated to reflux and stirred overnight. Upon arrival the solution was cooled to room temperature, diluted with dichloromethane (300 mL) and washed with 1N sodium hydroxide solution (2×200mL). The organic layer was then washed with water (200 mL) and concentrated to dryness on a rotary evaporator. The crude material was then redissolved in dioxane (450 mL) and water (50 mL) and stirred at room temperature. Silver nitrate (65.7 g, 387 mMol) was added and the material allowed to stir overnight. Upon arrival the reaction mixture was filtered and the solids washed with ethyl acetate. The filtrate was extracted with ethyl acetate (3×200 mL). The organics were dried with magnesium sulfate, filtered, and concentrated on a rotary evaporator. Purification by flash column silica gel chromatography 30% ethyl acetate in hexane as the eluant yielded a still impure product that was recolumned using 50% dichloromethane in hexane to give 5.7 g (35% yield) of 3-Fluoro-4-nitro-benzaldehyde. 1H NMR (DMSO-d6): δ=10.09 (s, 1H), 8.36 (m, 1H), 8.07 (dd, 1H, J=11, 1.5 Hz), 7.96 (dd, 1H, J=8.3, 1.5 Hz).

1. customIn a round bottom flask under nitrogen was combined
2. temperaturereflux condenser
3. temperaturethe solution heated
4. temperatureto reflux
5. stirringstirred overnight
6. temperatureUpon arrival the solution was cooled to room temperature
7. washwashed with 1N sodium hydroxide solution (2×200mL)
8. washThe organic layer was then washed with water (200 mL)
9. concentrationconcentrated to dryness on a rotary evaporator
10. dissolutionThe crude material was then redissolved in dioxane (450 mL)
11. stirringwater (50 mL) and stirred at room temperature
12. stirringto stir overnight
13. filtrationUpon arrival the reaction mixture was filtered
14. washthe solids washed with ethyl acetate
15. extractionThe filtrate was extracted with ethyl acetate (3×200 mL)
16. dry with materialThe organics were dried with magnesium sulfate
17. filtrationfiltered
18. concentrationconcentrated on a rotary evaporator
19. customPurification by flash column silica gel chromatography 30% ethyl acetate in hexane as the eluant
20. customyielded a still impure product that

ORD record

ord-6da41c9dbce644aab82232270655b9df

Source dataset

uspto-grants-2010_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07696210B2