Dimethylformamide → Acyclovirvalericester

HRID 1089681

Reaction equation

HRID 1089681 reaction equation
[CH:1]1[N:5]([CH2:6][O:7][CH2:8][CH2:9][OH:10])[C:4]2[N:11]=[C:12]([NH2:16])[N:13]=[C:14]([OH:15])[C:3]=2[N:2]=1.CN(C)C=O.[C:22](Cl)(=[O:27])[CH2:23][CH2:24][CH2:25][CH3:26]>CN(C)C1C=CN=CC=1.CO.O>[C:22]([O:10][CH2:9][CH2:8][O:7][CH2:6][N:5]1[CH:1]=[N:2][C:3]2[C:14](=[O:15])[NH:13][C:12]([NH2:16])=[N:11][C:4]1=2)(=[O:27])[CH2:23][CH2:24][CH2:25][CH3:26]

Participants

6

Reactant 3

HCID 6228DimethylformamideHCID 61186Valeryl chlorideHCID 178508933HCID 178508933, compound

Product 1

HCID 135524524AcyclovirvalericesterYield 85.1%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 22242641Methanol--water (1/1)Solvent

Conditions

Temperature
5 °C

Procedure

A mixture of acyclovir prepared according to UK Patent No. 1523865 (3.11 moles), 4-dimethylaminopyridine (4.91 moles) and dimethylformamide (5.6 L) was stirred under nitrogen with heating on steam bath to give a homogeneous solution. On cooling to room temperature valeryl chloride (4.91 moles) was added dropwise while the temperature was maintained at 20°-25° C. Progress of the reaction was monitored by HPLC (Partisil ODS-3, methanol:water 50:50) and the reaction was terminated when the level of residual acyclovir was less than 0.5% (AUC). The mixture was cooled to 5° C., filtered and the cake was washed with dimethylformamide (200 ml). The combined filtrates were diluted with absolute ethanol (1 L), stirred for two hours at ambient temperature and concentrated to a thick oil. Methanol (16 L) was added and the resulting suspension was refluxed for 1.5 hours, cooled to 5° C. and filtered. The crude product was washed with methanol (200 mL) and dried under vacuum to constant weight to give 819 g (85.1% yield) of 9-(2-valeryloxyethoxymethyl) guanine, M.p. 215°-217° C.

Workup

  1. customprepared
  2. temperaturewith heating on steam bath
  3. customto give a homogeneous solution
  4. additionwas added dropwise while the temperature
  5. temperaturewas maintained at 20°-25° C
  6. customthe reaction was terminated when the level of residual acyclovir
  7. filtrationfiltered
  8. washthe cake was washed with dimethylformamide (200 ml)
  9. additionThe combined filtrates were diluted with absolute ethanol (1 L)
  10. concentrationconcentrated to a thick oil
  11. additionMethanol (16 L) was added
  12. temperaturethe resulting suspension was refluxed for 1.5 hours
  13. temperaturecooled to 5° C.
  14. filtrationfiltered
  15. washThe crude product was washed with methanol (200 mL)
  16. customdried under vacuum to constant weight

Sources & evidence

ORD record
ord-f7df73bf6c844dc890797c17757fe548
Source dataset
uspto-grants-1992_01
Patent number
US05079252

Linked notes

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