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

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Reaction Conditions

Reaction Steps

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+).

Provenance & Evidence