[H-].[Na+].[Cl:3][C:4]1[CH:9]=[C:8]([OH:10])[CH:7]=[CH:6][N:5]=1.OC1C=CC=CN=1.[F:18][C:19]1[CH:24]=[C:23](F)[C:22]([F:26])=[CH:21][C:20]=1[N+:27]([O-:29])=[O:28]>CN(C=O)C>[Cl:3][C:4]1[CH:9]=[C:8]([O:10][C:23]2[CH:24]=[C:19]([F:18])[C:20]([N+:27]([O-:29])=[O:28])=[CH:21][C:22]=2[F:26])[CH:7]=[CH:6][N:5]=1Sodium hydride (60% by weight in mineral oil) (3.08 g, 77 mmol) was placed in a 500 mL round bottom flask flushed with argon. DMF (140 mL) was added and the mixture was cooled in an ice bath. 2-Chloro-4-hydroxypyridine (7.68 g, 59.3 mmol) was then added slowly over 45 minutes. After addition of the hydroxypyridine was complete 2,4,5-trifluoronitrobenzene (10.5 g, 59.3 mmol) was added as a solution in DMF (29 mL). The mixture was warmed to room temperature and stirred for 18 hours. The reaction mixture was concentrated under reduced pressure to remove the majority of DMF in the mixture, and was then partitioned between ethyl acetate (300 mL) and 10% aqueous lithium chloride (150 mL). A precipitate formed which was removed via suction filtration and then the layers were separated. The organic layer was washed with additional 10% aqueous lithium chloride (2×150 mL), saturated aqueous sodium bicarbonate (150 mL) and brine (150 mL). The organic layer was dried over magnesium sulfate and evaporated to yield a dark red solid which was purified by silica gel chromatography (10 to 30% ethyl acetate/hexane) to give 2-chloro-4-(2,5-difluoro-4-nitrophenoxy)pyridine (13.56 g, 80% yield) as a yellow solid. 1H NMR (400 MHz, DMSO-d6): δ 8.45 (dd, 1H), 8.39 (d, 1H), 7.87 (dd, 1H), 7.39 (d, 1H), 7.24 (dd, 1H); MS (ESI) m/z: 287.0 (M+H+).
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