Hydrochloric Acid → 4-((5-Chloro-6-isopropoxypyridin-3-yl)methoxy)-2,5-difluorobenzoic acid

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Reaction Conditions

Reaction Steps

To a solution of 4-((5,6-dichloropyridin-3-yl)methoxy)-2,5-difluorobenzoic acid (Preparation 14, 210 mg, 0.67 mmol) in THF (5 mL) was added an oil dispersion of NaH (60%, 157 mg, 3.93 mmol) followed by iso-propanol (5 mL) and the reaction mixture was warmed to 80° C. and stirred for 18 hours under a nitrogen atmosphere. Aqueous hydrogen chloride solution (1 M, 20 mL) was added and the mixture extracted with EtOAc (3×30 mL). The combined organics were dried over magnesium sulfate and the solvent was removed in vacuo. The resulting crude was purified by reverse phase chromatography eluting with H2O/MeCN/HCOOH (95/5/0.1 to 5/95/0.1, Biotage™ 40 g C18-silica gel) to yield the title compound (105 mg, 46%).

Provenance & Evidence