反应详情

Anhydrous N,N-dimethylformamide (150 mL) was added to 60% NaH in mineral oil (2.72 g, 67.9 mmol) under an atmosphere of argon. The mixture was cooled in an ice bath and stirred. To this suspension was added, portion-wise, a solution of 2-chloropyridin-4-ol (8 g, 61.8 mmol) in DMF (30.0 mL). The reaction mixture was stirred cold for 5 minutes and the cooling bath was removed. The reaction mixture was warmed to RT and stirred for 20 minutes. 1,2,4-trifluoro-5-nitrobenzene (13.12 g, 74.1 mmol) was added and the reaction mixture heated at 90° C. for 3 hours. The reaction mixture was cooled to RT. The mixture was concentrated to dryness. EtOH (50 mL) and MeOH (20 mL) were added and the sample was stirred with gentle warming and then cooled to RT. The yellow solid was collected by filtration, and rinsed with EtOH (50 mL) and hexanes (20 mL). The solid was dried under vacuum overnight to provide 2-chloro-4-(2,5-difluoro-4-nitrophenoxy)pyridine as a yellow solid (11.68 g, 63% yield). 1H NMR (400 MHz, DMSO-d6): δ 8.48 (dd, J=10.2, 7.0 Hz, 1H), 8.41 (d, J=5.6 Hz, 1H), 7.90 (dd, J=11.6, 6.7 Hz, 1H), 7.41 (d, J=2.1 Hz, 1H), 7.26 (dd, J=5.6, 2.4 Hz, 1H); MS (ESI): m/z 287.0 [M+H]+

1. temperatureThe mixture was cooled in an ice bath
2. additionTo this suspension was added
3. stirringThe reaction mixture was stirred cold for 5 minutes
4. customthe cooling bath was removed
5. stirringstirred for 20 minutes
6. temperaturethe reaction mixture heated at 90° C. for 3 hours
7. temperatureThe reaction mixture was cooled to RT
8. concentrationThe mixture was concentrated to dryness
9. additionEtOH (50 mL) and MeOH (20 mL) were added
10. stirringthe sample was stirred
11. temperaturewith gentle warming
12. temperaturecooled to RT
13. filtrationThe yellow solid was collected by filtration
14. washrinsed with EtOH (50 mL) and hexanes (20 mL)
15. customThe solid was dried under vacuum overnight