反应详情

To 60% NaH in mineral oil (0.119 g, 2.97 mmol), under an atmosphere of argon, was added anhydrous DMF (3 mL) and the slurry was cooled in an ice bath. To this suspension was added, in portions, a solution of 2-chloropyridin-4-ol (0.35 g, 2.70 mmol) in DMF (2 mL). The reaction mixture was stirred cold for 5 minutes and then allowed to warm to RT and stirred for 20 minutes. 1,5-difluoro-2-methyl-4-nitrobenzene (0.514 g, 2.97 mmol) was added and the reaction mixture heated at 90° C. for 3 hours, cooled to RT, quenched with water and the mixture was extracted with EtOAc (3×). The combined organic phases were washed with brine, dried (Na2SO4), concentrated in vacuo and purified by silica gel column chromatography (EtOAc/hexanes) to obtain 2-chloro-4-(5-fluoro-2-methyl-4-nitrophenoxy)pyridine (0.48 g, 63% yield) MS (ESI) m/z: 283.0 (M+H+).

1. temperaturethe slurry was cooled in an ice bath
2. additionTo this suspension was added, in portions
3. stirringstirred for 20 minutes
4. temperaturethe reaction mixture heated at 90° C. for 3 hours
5. temperaturecooled to RT
6. customquenched with water
7. extractionthe mixture was extracted with EtOAc (3×)
8. washThe combined organic phases were washed with brine
9. dry with materialdried (Na2SO4)
10. concentrationconcentrated in vacuo
11. custompurified by silica gel column chromatography (EtOAc/hexanes)