3-Hydroxypyridine → 4-(Pyridin-3-yloxy)benzonitrile

Temperature

120 °C

To a solution of 3-hydroxypyridine (2.1 g, 0.02 mmol) in NMP (20 mL) were added cesium carbonate (7.2 g, 0.02 mmol), 4-bromobenzonitrile (2.0 g, 0.01 mmol), 2,2,6,6-tetramethyl-3,5-heptanedione (0.23 mL, 0.001 mmol) and copper chloride (0.54 g, 0.005 mmol) at room temperature. The suspension was stirred at 120° C. for 6.5 hours. The reaction was cooled to room temperature and diluted with EtOAc (75 mL). The suspension was filtered and the filtrate washed with H2O (4×100 mL). Combined aqueous washes were extracted once with EtOAc (100 mL). Combined organic layer was washed with brine, dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The product was purified by column chromatography (10-20% acetone in hexanes) to provide the title compound as an orange oil (1.53 g, 71%). 1H NMR (300 MHz, CDCl3): δ 8.45-8.60 (m, 2H), 7.67 (d, 2H), 7.28-7.42 (m, 2H), 7.07 (d, 2H).

1. temperatureThe reaction was cooled to room temperature
2. filtrationThe suspension was filtered
3. washthe filtrate washed with H2O (4×100 mL)
4. extractionCombined aqueous washes were extracted once with EtOAc (100 mL)
5. washCombined organic layer was washed with brine
6. dry with materialdried over anhydrous Na2SO4
7. filtrationfiltered
8. concentrationconcentrated under reduced pressure
9. customThe product was purified by column chromatography (10-20% acetone in hexanes)

ORD record

ord-fbaa4fea4aac40aeb0a011f1f8f16d37

Source dataset

uspto-grants-2011_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07968570B2