2,2,2-Trifluoroethanol → 5-Bromo-6-(2,2,2-trifluoro-ethoxy)-pyridine-2-carboxylic acid

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Reaction Steps

In a 25 mL round-bottomed flask, 5-bromo-6-chloropicolinic acid (433 mg, 1.83 mmol) and powdered potassium hydroxide (411 mg, 7.32 mmol) were combined with DMSO (1.9 ml) to give a colorless solution which was stirred at room temperature for 15 min. 2,2,2-trifluoroethanol (275 mg, 198 μl, 2.75 mmol, Eq: 1.5) was added. The reaction mixture was stirred for 24 h at ambient temperature. Since the reaction was complete, 0.75 extra equivalents of 2,2,2-trifluoroethanol was added and the reaction was stirred 48 h at ambient temperature. The reaction mixture was poured onto 1 M HCl/ice water (1×20 mL), extracted with iPrOAc (2×25 mL). The organic layers were dried over Na2SO4 and filtered, removed under reduced pressure to give the title compound as a white solid after recrystallization from CH2Cl2 and heptane (409 mg, 1.36 mmol, 74.4% yield), MS (EI): m/e=299.9 [M+H]+.

Provenance & Evidence