反应详情

温度

95 °C

N-[4-(Cyano-dimethyl-methyl)-benzyl]-2-(4-fluoro-phenoxy)-nicotinamide (12.22 g) was placed in a sealable tube with anyhdrous toluene (10 mL). Trimethylsilyl azide (8.0 mL) and dimethyltin oxide (1.29 g) were then added. The reaction mixture was heated to 95° C. for 17 h, then allowed to cool to ambient temperature. Excess methanol was added and the mixture was concentrated to dryness in vacuo. Methanol was again added and evaporated. To the crude product were added ethyl acetate (200 mL) and and saturated aqueous sodium bicarbonate (100 mL) and water (100 mL). The aqueous layer was collected, and the organic layer extracted with 50% sodium bicarbonate twice (100 mL). The combined aqueous portions were separated and brought to pH 3 with conc. hydrochloric acid. The aqueous solution was then re-extracted with ethyl acetate (5×300 mL). The combined organics were dried over magnesium sulfate, filtered, and concentrated to dryness in vacuo. The crude product was purified by recrystallization (ethanol) to yield the title compound (5.36 g).

1. temperatureto cool to ambient temperature
2. concentrationthe mixture was concentrated to dryness in vacuo
3. additionMethanol was again added
4. customevaporated
5. additionTo the crude product were added ethyl acetate (200 mL) and and saturated aqueous sodium bicarbonate (100 mL) and water (100 mL)
6. customThe aqueous layer was collected
7. extractionthe organic layer extracted with 50% sodium bicarbonate twice (100 mL)
8. customThe combined aqueous portions were separated
9. extractionThe aqueous solution was then re-extracted with ethyl acetate (5×300 mL)
10. dry with materialThe combined organics were dried over magnesium sulfate
11. filtrationfiltered
12. concentrationconcentrated to dryness in vacuo
13. customThe crude product was purified by recrystallization (ethanol)