反应详情

温度

55 °C

To a solution of 6-chloro-2-isobutoxy-nicotinamide (3, 2.39 g, 10.4 mmol) in acetonitrile (anhydrous, 150 mL) were added pyridine (6.75 mL, 83.5 mmol) and POCl3 (3.82 mL, 41.7 mmol). The reaction was heated at 55° C. for 3 hours. After cooling to room temperature, NaOH solution (10% aq.) was slowly added till pH 9. EtOAc (60 mL) was added and the layers separated. The aqueous layer was extracted with EtOAc (2×60 mL). The combined organic layer was dried over MgSO4, filtered, and concentrated in vacuo. Purification was accomplished by silica gel chromatography, eluting with 2%-30% EtOAc/hexanes gradient, to afford 2 g (91% yield) of the title product.

1. temperatureAfter cooling to room temperature
2. customthe layers separated
3. extractionThe aqueous layer was extracted with EtOAc (2×60 mL)
4. dry with materialThe combined organic layer was dried over MgSO4
5. filtrationfiltered
6. concentrationconcentrated in vacuo
7. customPurification
8. washeluting with 2%-30% EtOAc/hexanes gradient