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

HRID 2105685Notes

Reaction equation

HRID 2105685 reaction equation
C[O:2][C:3]([C:5]12[CH2:12][CH2:11][C:8]([C:13]3[NH:21][C:20]4[C:19](=[O:22])[N:18]([CH2:23][CH2:24][CH3:25])[C:17](=[O:26])[N:16]([CH2:27][CH2:28][CH3:29])[C:15]=4[N:14]=3)([CH2:9][CH2:10]1)[CH2:7][CH2:6]2)=[O:4].O.C1(C)C=CC=CC=1>[OH-].[K+]>[O:26]=[C:17]1[N:16]([CH2:27][CH2:28][CH3:29])[C:15]2[N:14]=[C:13]([C:8]34[CH2:11][CH2:12][C:5]([C:3]([OH:4])=[O:2])([CH2:10][CH2:9]3)[CH2:6][CH2:7]4)[NH:21][C:20]=2[C:19](=[O:22])[N:18]1[CH2:23][CH2:24][CH3:25]

Participants

5

Reactant 3

HCID 962WaterHCID 1140TolueneHCID 98440604-(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

Product 1

HCID 98865894-(2,6-dioxo-1,3-dipropyl-2,3,6,7-tetrahydro-1H-purin-8-yl)-bicyclo[2.2.2]octane-1-carboxylic acid

Reagents, catalysts & solvents 1

HCID 14797Potassium HydroxideSolvent

Conditions

Temperature
17.5 °C

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-51bdee2281f44d1eb4c5c74f58b052bd
Source dataset
uspto-grants-2009_08
Patent number
US07579354B2

Reaction notes

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