反应详情

温度

90 °C

5-Chloro-6-isobutoxypyridin-3-ol (Preparation 16, 0.124 g, 0.62 mmol) and potassium carbonate (0.28 g, 2.03 mmol) were suspended in DMSO (3.0 mL). Then 3-cyano-4-fluorobenzoic acid (0.0835 g, 0.51 mmol) was added portionwise. The reaction was then stirred at 90° C. under nitrogen for 16 hours, diluted in EtOAc (15 mL) and washed twice with an aqueous solution of HCl (2.0 M, 10 mL). The organic layer was then dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by reverse phase column chromatography (ISCO®, gradient of 5-95% acetonitrile in water, 13 g C18 column) to afford the title compound as an orange oil (0.21 g, 120%):

1. washwashed twice with an aqueous solution of HCl (2.0 M, 10 mL)
2. dry with materialThe organic layer was then dried over sodium sulfate
3. filtrationfiltered
4. concentrationconcentrated in vacuo
5. customThe residue was purified by reverse phase column chromatography (ISCO®, gradient of 5-95% acetonitrile in water, 13 g C18 column)