Nitric Acid → HCID 86083513, compound

Temperature

0 °C

A solution of N-(2-chloro-4,5-difluorophenyl)acetamide (4.69 g, 22.8 mmol) in acetic acid (4.5 mL) and concentrated sulfuric acid (15 ml) was cooled to 0° C. To the solution was added a mixture of fuming nitric acid (2 mL) and acetic acid (0.5 mL). After stirring for 1.5 h at 0° C., the mixture was poured into ice. A precipitate formed, and it was collected by filtration. The filtrate was extracted with ether, and the organic phase was dried over magnesium sulfate, filtered, and concentrated to sticky yellow syrup. The solid and the syrup were combined, and to the resulting residue was added concentrated hydrochloric acid (30 mL). This mixture was heated to 120° C. for 1.25 h. It was then cooled to rt and subsequently poured onto ice. The aqueous solution was extracted with ethyl acetate. The organics were washed with saturated sodium bicarbonate, dried over magnesium sulfate, filtered, and concentrated. The residue was purified by flash chromatography (80% hexanes:20% ethyl acetate) to provide the desired 6-chloro-3,4-difluoro-2-nitroaniline (3.30 g, 15.8 mmol, 69% yield). 1H NMR (400 MHz, CDCl3): 7.43 (dd, 1H), 5.86 (br s, 2H); GCMS for C6H3ClF2N2O2: 208 (M+).

1. additionTo the solution was added
2. additionthe mixture was poured into ice
3. customA precipitate formed
4. filtrationit was collected by filtration
5. extractionThe filtrate was extracted with ether
6. dry with materialthe organic phase was dried over magnesium sulfate
7. filtrationfiltered
8. concentrationconcentrated to sticky yellow syrup
9. additionto the resulting residue was added concentrated hydrochloric acid (30 mL)
10. temperatureThis mixture was heated to 120° C. for 1.25 h
11. temperatureIt was then cooled to rt
12. additionsubsequently poured onto ice
13. extractionThe aqueous solution was extracted with ethyl acetate
14. washThe organics were washed with saturated sodium bicarbonate
15. dry with materialdried over magnesium sulfate
16. filtrationfiltered
17. concentrationconcentrated
18. customThe residue was purified by flash chromatography (80% hexanes:20% ethyl acetate)

ORD record

ord-d4a33752af354d9a8020e02ab3b57676

Source dataset

uspto-grants-2010_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07846959B2