Phosphoric Acid → 5-Chloro-1,2-difluoro-3-nitrobenzene

Temperature

0 °C

A solution of 6-chloro-3,4-difluoro-2-nitroaniline (3.30 g, 15.8 mmol) in concentrated sulfuric acid (8.3 mL) was stirred at rt for 3 h and was then cooled to 0° C. A solution of sodium nitrite (1.3 g, 18.8 mmol) concentrated sulfuric acid (6.7 mL) was added slowly followed by phosphoric acid (85%, 15 mL) added drop wise. A dark brown precipitate formed, and the resulting slurry was stirred for 1 h at 0° C. A suspension of copper(I) oxide (2.4 g, 30 mmol) and sodium hypophosphite hydrate (5.6 g, 64 mmol) in water (6.7 mL) was then added slowly with the temperature remaining at 0° C. Substantial gas evolution was observed during the addition. When the reaction was complete, the mixture was diluted with water and ether. Celite was added to help adsorb insoluble solids. The mixture was filtered, and the filtrate was partitioned. The organic phase was dried over magnesium sulfate, filtered, and concentrated in vacuo. The residue was purified by flash chromatography (90% hexanes: 10% ethyl acetate) to provide the desired 5-chloro-1,2-difluoro-3-nitrobenzene (1.62 g, 8.4 mmol, 53% yield) as a yellow crystalline solid. 1H NMR (400 MHz, CDCl3): 7.88 (m, 1H), 7.53 (m, 1H); GCMS for C6H2ClF2NO2: 193 (M+).

1. additionadded drop wise
2. customA dark brown precipitate formed
3. additionwas then added slowly with the temperature
4. customremaining at 0° C
5. additionSubstantial gas evolution was observed during the addition
6. additionCelite was added
7. filtrationThe mixture was filtered
8. customthe filtrate was partitioned
9. dry with materialThe organic phase was dried over magnesium sulfate
10. filtrationfiltered
11. concentrationconcentrated in vacuo
12. customThe residue was purified by flash chromatography (90% hexanes: 10% ethyl acetate)

ORD record

ord-11cac65ab91144ebbb851c92dfd93bf7

Source dataset

uspto-grants-2014_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08697737B2