反应详情

温度

20 °C

Nitrile 6 (101 g) and methanol (1.01 L, 10 vol.) were charged to a 3-L flask equipped with stir bar and thermocouple. Concentrated H2SO4 (175 mL, 10.0 equiv.) was added drop wise to the solution over 15 minutes while maintaining a temperature below 60° C. Followed by 30% fuming sulfuric acid (124 mL) was added drop wise to the solution while maintaining a temperature below 60° C. The solution was then heated to reflux with a heating mantle and stirred overnight. When the reaction was deemed complete, it was cooled to 20° C. In a second flask (22 L), saturated sodium bicarbonate (10.7 L) and dichloromethane (1.1 L) were charged and cooled to 15° C. While maintaining a temperature below 20° C., the reaction mixture was added to the sodium bicarbonate/dichloromethane mixture. The quench was stirred for 15 minutes and the phases were separated. The aqueous phase was extracted with dichloromethane (1×550 mL, 1×300 mL). The combined organics were dried with magnesium sulfate and concentrated to dryness to give 105 g of an orange solid (94% crude yield, 97.7% AUC by HPLC).

1. customequipped
2. temperaturewhile maintaining a temperature below 60° C
3. temperaturewhile maintaining a temperature below 60° C
4. temperatureThe solution was then heated
5. temperatureto reflux with a heating mantle
6. stirringstirred overnight
7. temperaturecooled to 15° C
8. temperatureWhile maintaining a temperature below 20° C.
9. stirringThe quench was stirred for 15 minutes
10. customthe phases were separated
11. extractionThe aqueous phase was extracted with dichloromethane (1×550 mL, 1×300 mL)
12. dry with materialThe combined organics were dried with magnesium sulfate
13. concentrationconcentrated to dryness