Acetic Acid → 6-(Benzyloxy)pyridine-3-carboxylic acid

Participants

Reaction Conditions

Reaction Steps

Oil-free NaH (1.9 g,~5 eq.) was suspended in DMF (30 ml) and the suspension was cooled in an ice bath. Benzyl alcohol (8.6 ml, ~5.2 eq.) was added slowly to the suspension via syringe. The resulting reaction mixture was stirred at 0° C. for 20 min., after which it was transferred to a precooled (0° C.) solution of 6-chloronicotinic acid (2.5 g, 15.9 mmol) in DMF (30 ml). Additional DMF (20 ml) was added to the reaction mixture to facilitate stirring. The reaction mixture was refluxed for 2 hours. Aqueous acetic acid 5% (by volume) was added to the cooled reaction mixture, and the resultant acidic mixture was extracted (3x) with ethyl acetate. The organic layers were combined, washed with brine and the solvent was removed to give a yellow liquid, from which a white solid was obtained after addition of water. Recrystallization from acetone/water gave 6-benzyloxynicotinic acid (4, Scheme I, 88% yield) as colorless needles.

Provenance & Evidence