3-Bromo-5-hydroxypyridine → 5-Hydroxypyridine-3-carbonitrile

Temperature

135 °C

A mixture of 5-bromo-pyridin-3-ol (9.94 mL, 54.0 mmol) and CuCN (7.4 g, 82.62 mmol) in DMF (20 mL) was heated at 135° C. for 5 hour. DMF was removed under reduced pressure, the residue was diluted with NH4OH (10 mL) at 0° C. The mixture was bubbled with ammonia gas for 1 hour, cooled to 0° C. and acidified with conc. HCl (35 mL) until pH reached to ˜4. The resulting mixture was extracted with EtOAc (5×100 mL). The organic layer was washed with water (2×100 mL) and brine (2×100 mL) solution, dried over anhydrous Na2SO4, filtered, and concentrated to give yellow solid. Purification was accomplished by flash chromatography on silica gel using 5-25% EtOAc/hexanes gradient elution to yield the title compound (2.5 g, 39%) as a yellow solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 10.78 (s, 1H), 8.46 (d, J=2.0 Hz, 1H), 8.41 (d, J=2.7 Hz, 1H), 7.61-7.57 (m, 1H).

1. customDMF was removed under reduced pressure
2. additionthe residue was diluted with NH4OH (10 mL) at 0° C
3. customThe mixture was bubbled with ammonia gas for 1 hour
4. temperaturecooled to 0° C.
5. extractionThe resulting mixture was extracted with EtOAc (5×100 mL)
6. washThe organic layer was washed with water (2×100 mL) and brine (2×100 mL) solution
7. dry with materialdried over anhydrous Na2SO4
8. filtrationfiltered
9. concentrationconcentrated
10. customto give yellow solid
11. customPurification
12. washwas accomplished by flash chromatography on silica gel using 5-25% EtOAc/hexanes gradient elution

ORD record

ord-7d36cc4b7353407fbe459c65df466ca9

Source dataset

uspto-grants-2016_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09416146B2