反应详情

温度

17.5 °C

4-(2,6-Dioxo-1,3-dipropyl-2,3,6,7-tetrahydro-1H-purin-8-yl)-bicyclo[2.2.2]octane-1-carboxylic acid methyl ester (VIII, Example 84a) in the potassium hydroxide environment is heated at reflux for 2 to 3 hr until complete as measured by NMR. The mixture is then cooled to 10 to 25° C. Water (11.16 vol) is added followed by toluene (1.25 vol) and the contents are stirred vigorously for 5 to 15 minutes. The layers are separated. Toluene (1.25 vol) is added to the aqueous layer and the mixture is stirred vigorously for a 5 to 15 minutes. The layers are separated. Toluene (1.25 vol) is added to the aqueous layer, stirred vigorously for 5 to 15 minutes and the layers are separated. The aqueous phase is then cooled to between 0 and 10° C. and acidified with concentrated hydrochloric acid. (0.74 vol), maintaining the temperature below 10° C. The mixture is stirred at between 0 and 10° C. for 60 to 90 minutes. The solid is collected by filtration and dried under reduced pressure to give the title compound.

1. temperatureat reflux for 2 to 3 hr until complete
2. customThe layers are separated
3. additionToluene (1.25 vol) is added to the aqueous layer
4. stirringthe mixture is stirred vigorously for a 5 to 15 minutes
5. customThe layers are separated
6. additionToluene (1.25 vol) is added to the aqueous layer
7. stirringstirred vigorously for 5 to 15 minutes
8. customthe layers are separated
9. temperatureThe aqueous phase is then cooled to between 0 and 10° C.
10. temperature(0.74 vol), maintaining the temperature below 10° C
11. stirringThe mixture is stirred at between 0 and 10° C. for 60 to 90 minutes
12. filtrationThe solid is collected by filtration
13. customdried under reduced pressure