Sodium Carbonate → 5-Chloro-6-phenyl-3-pyridinol

Temperature

80 °C

To a solution of 6-bromo-5-chloropyridin-3-ol (Preparation 239, 100 mg, 0.48 mmol), and phenylboronic acid (117 mg, 0.96 mmol) in 1,4-dioxane (5 mL) under nitrogen was added 2M aqueous Na2CO3 solution (1 mL) and palladium tetrakistriphenylphosphine (28 mg, 0.024 mmol). The mixture was stirred at 80° C. for 3.5 hours. The reaction mixture was allowed to cool to room temperature and partitioned between water and EtOAc. The desired product was in the aqueous phase (pH ˜11). The organic phase was washed with 10 wt % aqueous NaOH solution (2×15 mL). The combined aqueous phases were neutralised with 1N aqueous citric acid solution and extracted with EtOAc (4×30 mL). The combined organic phases were washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo to give a crude product. The crude product was purified by silica gel chromatography eluting with 0-30% EtOAc in heptane to give the title compound (67 mg, 68%) as a white solid.

1. temperatureto cool to room temperature
2. custompartitioned between water and EtOAc
3. washThe organic phase was washed with 10 wt % aqueous NaOH solution (2×15 mL)
4. extractionextracted with EtOAc (4×30 mL)
5. washThe combined organic phases were washed with brine
6. dry with materialdried over Na2SO4
7. filtrationfiltered
8. concentrationconcentrated in vacuo
9. customto give a crude product
10. customThe crude product was purified by silica gel chromatography
11. washeluting with 0-30% EtOAc in heptane

ORD record

ord-7d967e51477e4ed1b8bf13d1b319c5c2

Source dataset

uspto-grants-2013_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08592629B2