Dimethylformamide → 3-((5-Chloropyridin-2-yl)oxy)benzoic acid

Participants

Reaction Conditions

Reaction Steps

To a dimethylformamide (100 mL) solution of 3-hydroxy-benzoic acid methyl ester (3.5 g, 23 mmol) was added potassium t-butoxide (3.2 g, 28 mmol). Upon stirring the reaction at room temperature for 15 min, 2-bromo-5-chloro-pyridine was added. The reaction was heated to 130° C. for 15 h. Crude reaction mass was added to water, and extracted with diethyl ether to remove unhydrolyzed methyl ester, 3-(5-chloro-pyridin-2-yloxy)-benzoic acid methyl ester (2.5 g). The aqueous layer was acidified to pH 4.0 and product was extracted with ethyl acetate to give 3-(5-chloro-pyridin-2-yloxy)-benzoic acid (2.0 g). Saponification of methyl ester (2.5 g, 9.4 mmol) using NaOH (1.0 g, 25 mmol) in methanol:THF:water (1:1:1, 60 mL) furnished additional 2.0 g of 3-(5-chloro-pyridin-2-yloxy)-benzoic acid.

Provenance & Evidence