反应详情

A vigorously stirred slurry of nitrosonium tetrafluoroborate (3.53 g, 30.2 mM) in acetonitrile (50 ml) under an atmosphere of argon was cooled in an ice bath, and 3-amino-5-nitrobenzoic acid (5.0 g, 27.5 mM) was added in three portions. The temperature was then allowed to rise to ambient, and the mixture was stirred for 48 hours. 1,2-Dichlorobenzene (50 ml) was added, and acetonitrile distilled from the mixture at reduced pressure. The mixture was then heated to 170° for 30 minutes, when gas evolution had ended. After cooling, the mix was poured into dichloromethane (200 ml), and extracted with NaHCO3 solution. After back washing the aqueous phase with dichloromethane, it was acidified (2M hydrochloric acid), and organics extracted with ethyl acetate (2×100 ml). The combined organic layers were washed with brine, and dried over MgSO4. Crude product was purified by chromatography on silica, eluting with a gradient from dichloromethane/acetic acid (99:1) to dichloromethane/isopropanol/acetic acid (80:20:1), to give 3-fluoro-5-nitrobenzoic acid (3.26 g, 64%). Nmr (DHSO-d6): δ 8.14 (dm, 1H); 8.37 (dt, 1H); 8.46 (m, 1H).

1. distillationacetonitrile distilled from the mixture at reduced pressure
2. temperatureThe mixture was then heated to 170° for 30 minutes
3. temperatureAfter cooling
4. additionthe mix was poured into dichloromethane (200 ml)
5. extractionextracted with NaHCO3 solution
6. washAfter back washing the aqueous phase with dichloromethane, it
7. extractionorganics extracted with ethyl acetate (2×100 ml)
8. washThe combined organic layers were washed with brine
9. dry with materialdried over MgSO4
10. customCrude product was purified by chromatography on silica
11. washeluting with a gradient from dichloromethane/acetic acid (99:1) to dichloromethane/isopropanol/acetic acid (80:20:1)