Dimethylacetamide → 2-Cyano-6-methoxyisonicotinic acid

Participants

Reaction Conditions

Reaction Steps

Into an oven-dried microwave vial was added ethyl 2-chloro-6-methoxyisonicotinate (0.6 g, 2.78 mmol), zinc cyanide (392 mg, 3.34 mmol), zinc dust (36.4 mg, 0.2 mmol) and N,N-dimethylacetamide (10 mL). The vial was capped, evacuated, and filled with nitrogen. This process was repeated 3 times. Then the cap of the vial was removed and bis(tri-t-butylphosphine)palladium(0) (142 mg, 0.278 mmol) was added. The vial was capped again, evacuated, and filled with nitrogen (3×). The reaction mixture was heated to 95° C. and left stirring for 18 h. The reaction mixture was diluted with ethyl acetate (100 mL) and filtered through Celite. The filtrate was poured into a saturated aqueous solution of sodium bicarbonate (100 mL). Then the mixture was extracted with ethyl acetate (50 mL×3). The combined organics were washed with a saturated aqueous solution of ammonium chloride, washed with brine and dried over sodium sulfate. The solvent was removed under reduced pressure and the residue was purified via flash chromatography to afford 2-cyano-6-methoxyisonicotinic acid (260 mg, 45.3%) as a white solid. 1H NMR (400 MHz, CDCl3) δ 1.42 (s, 3H), 4.01 (s, 3H), 4.43 (s, 2H), 7.53 (s, 1H), 7.82 (s, 1H).

Provenance & Evidence