Acetic Acid → 2-Amino-9-[(2R)-4,4-diethoxy-2-(hydroxymethyl)butyl]-3,9-dihydro-6H-purin-6-one

HRID 458291Notes

Reaction equation

HRID 458291 reaction equation
[NH2:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[CH2:11][C@H:12]([CH2:21][OH:22])[CH2:13][CH:14]([O:18][CH2:19][CH3:20])[O:15][CH2:16][CH3:17])=[C:4](Cl)[N:3]=1.[OH-].[K+].C(O)(=[O:28])C>O>[CH2:16]([O:15][CH:14]([O:18][CH2:19][CH3:20])[CH2:13][C@@H:12]([CH2:21][OH:22])[CH2:11][N:8]1[CH:7]=[N:6][C:5]2[C:4](=[O:28])[NH:3][C:2]([NH2:1])=[N:10][C:9]1=2)[CH3:17]

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 14797Potassium HydroxideHCID 15515994HCID 15515994, compound

Product 1

HCID 1354445842-Amino-9-[(2R)-4,4-diethoxy-2-(hydroxymethyl)butyl]-3,9-dihydro-6H-purin-6-one

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
5 °C

Procedure

To the product of Example 30, step a) (22.5 kg, 65.4 moles) was added an aqueous solution of KOH (prepared by dissolving 12.9 kg of KOH in 225 kg of water). This mixture was refluxed for 16 hours. The reaction was cooled to about room temperature and filtered into a larger reactor equipped with a pH electrode standardized to pH 7–10. The filtered solution was cooled to 5° C. and the product precipitated by slow addition of dilute acetic acid solution (prepared by mixing glacial acetic acid (12.6 kg, 210 moles) with 75 kg of water and cooling the mixture to 5° C.) until the pH is between 7.5 and 9.0 (target 8.5). The resulting slurry was immediately filtered and the filter cake was recharged back to the reactor. The reactor was charged with 225 kg of distilled water. The mixture was heated to not more than 50° C. for 30 minutes, then cooled to 15±10° C. and stirred for 30 minutes. The resulting precipitate was filtered by vacuum filtration, rinsed with 50 kg of distilled water and dried in a vacuum oven at not more than 45° C. for not less than 8 hours to provide the desired product as a tan solid.

Workup

  1. temperatureThis mixture was refluxed for 16 hours
  2. temperatureThe reaction was cooled to about room temperature
  3. filtrationfiltered into a larger reactor
  4. customequipped with a pH electrode
  5. customthe product precipitated by slow addition of dilute acetic acid solution (
  6. customprepared
  7. temperaturecooling the mixture to 5° C.) until the pH is between 7.5 and 9.0 (target 8.5)
  8. filtrationThe resulting slurry was immediately filtered
  9. additionThe reactor was charged with 225 kg of distilled water
  10. temperatureThe mixture was heated to not more than 50° C. for 30 minutes
  11. temperaturecooled to 15±10° C.
  12. filtrationThe resulting precipitate was filtered by vacuum filtration
  13. washrinsed with 50 kg of distilled water
  14. customdried in a vacuum oven at not more than 45° C. for not less than 8 hours

Sources & evidence

ORD record
ord-e8086ad6d8244168a3bf096ea1469c27
Source dataset
uspto-grants-2007_03
Patent number
US07189849B2

Reaction notes

Loading…