Chlorosuccinimide → 6-Chloro-5-hydroxynicotinonitrile

Temperature

107 °C

A mixture of 5-hydroxy-nicotinonitrile (2.0 g, 16.66 mmol), and N-chlorosuccinimide (3.3 g, 25.0 mmol) in acetonitrile (33 mL) was heated in a sealed tube at 107° C. overnight. Acetonitrile was removed under reduced pressure, the residue was diluted with EtOAc (100 mL). The organic layer was washed with water (10 mL) and brine (2×10 mL), dried over Na2SO4, filtered, and concentrated to give brown oil. Purification was accomplished by flash chromatography on silica gel using 20-80% EtOAc/hexanes gradient elution to yield the title compound (0.55 g, 36%) as a yellow solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 11.70 (s, 1 H), 8.35 (d, J=2.0 Hz, 1 H), 7.67 (d, J=2.0 Hz, 1 H); MS (ES) m/z: 153 (M−1)−.

1. customAcetonitrile was removed under reduced pressure
2. additionthe residue was diluted with EtOAc (100 mL)
3. washThe organic layer was washed with water (10 mL) and brine (2×10 mL)
4. dry with materialdried over Na2SO4
5. filtrationfiltered
6. concentrationconcentrated
7. customto give brown oil
8. customPurification
9. washwas accomplished by flash chromatography on silica gel using 20-80% EtOAc/hexanes gradient elution

ORD record

ord-bb837aeb712c47a480b1e8027295a9ab

Source dataset

uspto-grants-2015_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09012431B2