Sodium hydride → 2-Chloro-4-(2,5-difluoro-4-nitrophenoxy)pyridine

Temperature

0 °C

Sodium hydride (136 mg, 3.4 mmol, 60% in mineral) was added to a 0° C. solution of 2-chloropyridin-4-ol (2 g, 15.4 mmol) in DMF (38 mL) under Ar. The mixture was stirred at 0° C. for 1 h. A solution of 1,2,4-trifluoro-5-nitrobenzene (626 mg, 3.1 mmol) in DMF (7.6 ml) was added and the reaction was stirred under Ar at 90° C. for 3 h. The mixture was cooled to RT and stirred overnight. The solvent was removed under reduced pressure and the crude product was partitioned between water (50 ml) and EtOAc (50 ml). The mixture was extracted with EtOAc (3×50 ml). The combined organic extracts were washed with brine, dried (Na2SO4), concentrated under reduced pressure and purified by silica gel column chromatography (hexanes/EtOAc) to yield 2-chloro-4-(2,5-difluoro-4-nitrophenoxy)pyridine (3.57 g, 81% yield). 1H NMR (400 MHz, DMSO-d6): δ 8.43-8.33 (m, 2H), 7.85-7.79 (m, 1H), 7.33 (d, 1H), 7.20-7.18 (m, 1H); MS (ESI) m/z: 287.0 (M+H+).

1. stirringthe reaction was stirred under Ar at 90° C. for 3 h
2. temperatureThe mixture was cooled to RT
3. stirringstirred overnight
4. customThe solvent was removed under reduced pressure
5. customthe crude product was partitioned between water (50 ml) and EtOAc (50 ml)
6. extractionThe mixture was extracted with EtOAc (3×50 ml)
7. washThe combined organic extracts were washed with brine
8. dry with materialdried (Na2SO4)
9. concentrationconcentrated under reduced pressure
10. custompurified by silica gel column chromatography (hexanes/EtOAc)

ORD record

ord-e8be375288e94c7a9aec9079df35ba7c

Source dataset

uspto-grants-2012_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08278331B2