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

Participants

Reaction Conditions

Reaction Steps

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, 1 H), 8.46 (d, J=2.0 Hz, 1 H), 8.41 (d, J=2.7 Hz, 1 H), 7.61-7.57 (m, 1 H).

Provenance & Evidence