Water → 4-(2,6-dioxo-1,3-dipropyl-2,3,6,7-tetrahydro-1H-purin-8-yl)-bicyclo[2.2.2]octane-1-carboxylic acid

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Reaction Conditions

Reaction Steps

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.

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