2,2,2-Trifluoroethanol → 2-(2,2,2-Trifluoroethoxy)pyridine-4-carboxylic acid

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Reaction Steps

2-Chloropyridine-4-carboxylic acid (200 mg, 1.27 mmol), potassium tert-butoxide (381 mg, 3.81 mmol) and 2,2,2-trifluoroethanol (2.6 mL) were charged to a sealed tube under nitrogen and stirred at 170 C for 3 h. 2,2,2-Trifluoroethanol (1 mL) was added and the reaction stirred at 170 C for 17 h. The mixture was evaporated under vacuum and the residue was dissolved in water (5 mL). 2M HCl was added to bring the solution to pH 5 and the mixture was extracted with DCM (3×10 mL). 2M HCl was then added to the aqueous layer to bring the solution to pH 3 and the mixture was extracted with DCM (4×6 mL). The combined organic extractions were washed with brine (5 mL), dried over sodium sulfate and evaporated under vacuum to afford the title compound as a white solid (210 mg, 75%). Method C HPLC-MS: MH+ requires m/z=222. Found: m/z=222, Rt=1.26 min (95%).

Provenance & Evidence