Sodium hydride → 2-Chloro-4-(2-chloro-5-fluoro-4-nitrophenoxy)pyridine

Participants

Reaction Conditions

Reaction Steps

Sodium hydride (60% in mineral oil) (0.620 g, 15.5 mmol) was placed in a 100 mL round bottom flask under argon. Dry DMF (30 mL) was added, followed by portion wise addition of 2-chloro-4-hydroxypyridine (1.339 g, 10.33 mmol) at 0° C. The mixture was stirred at 0° C. for 30 minutes, and then slowly warmed to RT. A solution of 5-chloro-2,4-difluoronitrobenzene (2 g, 10.33 mmol) in DMF (4.4 mL) was added to the suspension, and the mixture was placed in a 90° C. oil bath to heat for 15 hours under argon. The reaction mixture was then cooled to RT and diluted with ethyl acetate (100 mL), washed with 10% aqueous LiCl (3×100 mL) and brine (2×100 mL), dried (MgSO4) and purified via silica gel chromatography (ethyl acetate/hexanes) to yield 2-chloro-4-(2-chloro-5-fluoro-4-nitrophenoxy)pyridine as a bright yellow oil (1.415 g, 45% yield). 1H NMR (400 MHz, DMSO-d6): δ 8.56 (dd, 1H), 8.35 (dd, 1H), 7.88 (dd, 1H), 7.32 (dd, 1H), 7.18 (m, 1H); MS (ESI) m/z: 303.0 (M+H+).

Provenance & Evidence