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

関与物質

反応条件

反応手順

2-Chloro-4-hydroxypyridine (0.319 g, 2.460 mmol) was dissolved in DMF (10 mL) under argon and cooled to −15° C. Sodium hydride (60% in mineral oil) (0.148 g, 3.69 mmol) was added slowly and the mixture was stirred for 15 minutes. 5-Chloro-2,4-difluoronitrobenzene (0.5 g, 2.58 mmol) was then added all at once as a solution in DMF (2 mL). The reaction mixture stirred at −15° C. for 1 hour and then additional 5-chloro-2,4-difluoronitrobenzene (0.075 g) was added. The mixture stirred at −15° C. for an additional 15 hours and was then warmed to room temperature and diluted with ethyl acetate (100 mL) and washed with 10% aqueous lithium chloride (3×75 mL) and brine (75 mL). The organic layer was dried over magnesium sulfate and evaporated to yield an orange oil, which was then purified by silica gel chromatography (0 to 30% ethyl acetate/hexane) to give 2-chloro-4-(2-chloro-5-fluoro-4-nitrophenoxy)pyridine (0.64 g, 86% yield) as a light yellow oil. 1H NMR (400 MHz, DMSO-d6): δ 8.57 (dd, 1H), 8.36 (dd, 1H), 7.87 (dd, 1H), 7.32 (dd, 1H), 7.19 (m, 1H); MS (ESI) m/z: 303.0 (M+H+).

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