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

Temperature

-15 °C

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+).

1. stirringThe reaction mixture stirred at −15° C. for 1 hour
2. stirringThe mixture stirred at −15° C. for an additional 15 hours
3. temperaturewas then warmed to room temperature
4. washwashed with 10% aqueous lithium chloride (3×75 mL) and brine (75 mL)
5. dry with materialThe organic layer was dried over magnesium sulfate
6. customevaporated
7. customto yield an orange oil, which
8. customwas then purified by silica gel chromatography (0 to 30% ethyl acetate/hexane)

ORD record

ord-08f9b48c6536462e88f06e9414e1d125

Source dataset

uspto-grants-2014_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08637672B2