Hydrochloric Acid → 5-(2,2-Difluoro-ethoxy)-pyridine-2-carboxylic acid

Participants

Reaction Steps

To a mixture of 5-hydroxy-2-pyridinecarboxylic acid methyl ester (0.253 mL, 2.122 mmol), cesium carbonate (1.11 g, 3.40 mmol) and DMF (4.25 mL) was added 2,2-difluoroethyl trifluoromethanesulfonate (0.682 mL, 3.18 mmol). The reaction was stirred at ambient temperature for 3 hrs. The reaction was partitioned between water and ethyl acetate. The organic portion was concentrated and the residue was treated with 5 mL of THF and LiOH (Aq. 2N) (3.18 mL, 6.37 mmol). The reaction was stirred at ambient temperature for 16 hrs. The reaction was treated with 6N HCl until the pH reached ˜2 and then diluted with ethyl acetate. The organic portion was dried over Na2SO4, filtered and concentrated in vacuo to give the title compound (370 mg, 1.821 mmol, 86%) as a tan solid. MS m/z=204.1 (M+H).

Provenance & Evidence