Nicotinic Acid → 6-tert-Butylpyridine-3-carboxylic acid

Participants

Reaction Conditions

Reaction Steps

Nicotinic acid (1.0 g; 7.3 mmol) is dissolved in a mixture of water (10 mL) and conc. H2SO4 (0.5 mL) with stirring. tert-Butyl carboxylic acid is added, and the resulting crystalline slurry stirred under nitrogen. Catalytic AgNO3 and ammonium persulfate (140 mg; 0.61 mmol) are then added, the flask wrapped in aluminum foil to shield from light and the reaction heated to 90° C. for 3 hr. The reaction is cooled to 0° C., basified to pH 10 and extracted with EtOAc (4×50 mL). The pooled organic layers are washed with saturated sodium carbonate (2×50 mL) and brine, dried over anhydrous sodium sulfate and concentrated in vacuo. The resulting oil is purified by flash chromatography over silica gel to provide 6-tert-butyl-nicotinic acid (1.1 g) as a white solid.

Provenance & Evidence