Triethylamine → 9-(4-Acetoxy-3-acetoxymethylbut-l-yl)-2-aminopurine famciclovir

HRID 899486Notes

Reaction equation

HRID 899486 reaction equation
[C:1]([O:4][CH2:5][CH:6]([CH2:20][O:21][C:22](=[O:24])[CH3:23])[CH2:7][CH2:8][N:9]1[CH:17]=[N:16][C:15]2[C:10]1=[N:11][C:12]([NH2:19])=[N:13][C:14]=2Cl)(=[O:3])[CH3:2].C(N(CC)CC)C>[Pd].C(OCC)(=O)C>[C:1]([O:4][CH2:5][CH:6]([CH2:20][O:21][C:22](=[O:24])[CH3:23])[CH2:7][CH2:8][N:9]1[CH:17]=[N:16][C:15]2[C:10]1=[N:11][C:12]([NH2:19])=[N:13][CH:14]=2)(=[O:3])[CH3:2].[CH3:2][C:1]([O:4][CH2:5][CH:6]([CH2:20][O:21][C:22]([CH3:23])=[O:24])[CH2:7][CH2:8][N:9]1[C:10]2[N:11]=[C:12]([NH2:19])[N:13]=[CH:14][C:15]=2[N:16]=[CH:17]1)=[O:3]

Participants

5

Reactant 2

HCID 8471TriethylamineHCID 101551646-Chloro famciclovir

Product 1

HCID 702982549-(4-Acetoxy-3-acetoxymethylbut-l-yl)-2-aminopurine famciclovir

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

A mixture of 9-(4-acetoxy-3-acetoxymethylbut-l-yl)-2-amino-6-chloropurine (15.4 g, 43 mmole), 5% palladium on carbon (6.16 g), triethylamine (6.6 ml, 47 mmole) and ethyl acetate (77 ml) was stirred at 50° C. under a hydrogen atmosphere at 1 bar pressure in an autoclave for 3 to 5 hours. After completion of the reaction the mixture was removed from the autoclave which was washed out with ethyl acetate (30 ml) keeping the washings at 50° C. The main reaction mixture was filtered through a celite bed followed by the washings and finally with ethyl acetate (30 ml). Water (46 ml) was added to the combined ethyl acetate filtrate plus washings. The ethyl acetate was evaporated to dryness to leave a crude white solid. This was recrystallised from n-butanol (62 ml), stirring the cooled solution at 0 to 5° C. for 3 h before filtration. The product was filtered off and washed with the mother liquors. The solid was reslurried in n-heptane (50 ml) stirred for 30 minutes and filtered. The product was dried at 40° C. for 16 h under vacuum.

Workup

  1. customAfter completion of the reaction the mixture
  2. customwas removed from the autoclave which
  3. washwas washed out with ethyl acetate (30 ml)
  4. customat 50° C
  5. filtrationThe main reaction mixture was filtered through a celite bed
  6. additionWater (46 ml) was added to the combined ethyl acetate filtrate plus washings
  7. customThe ethyl acetate was evaporated to dryness
  8. customto leave a crude white solid
  9. customThis was recrystallised from n-butanol (62 ml)
  10. stirringstirring the cooled solution at 0 to 5° C. for 3 h
  11. filtrationbefore filtration
  12. filtrationThe product was filtered off
  13. washwashed with the mother liquors
  14. stirringstirred for 30 minutes
  15. filtrationfiltered
  16. customThe product was dried at 40° C. for 16 h under vacuum

Sources & evidence

ORD record
ord-8f2c62d8ce6d4f85a053305b2729ec45
Source dataset
uspto-grants-2008_04
Patent number
US07355043B2

Reaction notes

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