Methanol → 5'-O-acetyl-3'-O-benzyl-3'-(3-carbomethoxybenzoyl)-2'-deoxy-5-fluorouridine

HRID 466093Notes

Reaction equation

HRID 466093 reaction equation
[C:1]([O:4][CH2:5][C@H:6]1[O:10][C@@H:9]([N:11]2[CH:18]=[C:17]([F:19])[C:15](=[O:16])[NH:14][C:12]2=[O:13])[CH2:8][C@@H:7]1[O:20][CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)(=[O:3])[CH3:2].[C:28](Cl)(=[O:38])[C:29]1[CH:37]=[CH:36][CH:35]=[C:31]([C:32](Cl)=[O:33])[CH:30]=1.C(N(CC)CC)C.[CH3:47][OH:48]>O1CCOCC1>[C:1]([O:4][CH2:5][C@H:6]1[O:10][C@@H:9]([N:11]2[CH:18]=[C:17]([F:19])[C:15](=[O:16])[NH:14][C:12]2=[O:13])[CH2:8][C@:7]1([C:28](=[O:38])[C:29]1[CH:37]=[CH:36][CH:35]=[C:31]([C:32]([O:48][CH3:47])=[O:33])[CH:30]=1)[O:20][CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)(=[O:3])[CH3:2]

Participants

6

Reactant 4

HCID 887MethanolHCID 7451Isophthaloyl chlorideHCID 8471Triethylamine2×HCID 136874845'-O-acetyl-3'-O-benzyl-2'-deoxy-5-fluorouridine

Product 1

HCID 186481715'-O-acetyl-3'-O-benzyl-3'-(3-carbomethoxybenzoyl)-2'-deoxy-5-fluorouridineYield 69%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Procedure

To a solution of 3.00 g of 5'-O-acetyl-3'-O-benzyl-2'-deoxy-5-fluorouridine in 100 ml of dry dioxane were added 2.40 g of isophthaloyl chloride and 8.5 ml of triethylamine, and the mixture was refluxed for 2 hours. Then, to the reaction mixture were added 5 ml of methanol and a suspension of 9.60 ml of triethylamine in 100 ml of dry dioxane, and the mixture was refluxed for 2 hours. The insolubles were removed by filtration and the filtrate was concentrated. The residue was dissolved in 100 ml of ethyl acetate, and the solution was washed twice with 30 ml of saturated aqueous solution of sodium chloride. The ethyl acetate layer was dried over anhydrous sodium sulfate and concentrated. The residue was placed on a silica gel column to conduct a gradient elution using chloroform and mixtures of methanol (up to 2%) and chloroform. The fractions corresponding to the title compound were collected and concentrated to dryness, giving the title compound as a powder in a yield of 69%.

Workup

  1. temperaturethe mixture was refluxed for 2 hours
  2. temperaturethe mixture was refluxed for 2 hours
  3. customThe insolubles were removed by filtration
  4. concentrationthe filtrate was concentrated
  5. dissolutionThe residue was dissolved in 100 ml of ethyl acetate
  6. washthe solution was washed twice with 30 ml of saturated aqueous solution of sodium chloride
  7. dry with materialThe ethyl acetate layer was dried over anhydrous sodium sulfate
  8. concentrationconcentrated
  9. washa gradient elution
  10. customThe fractions corresponding to the title compound were collected
  11. concentrationconcentrated to dryness

Sources & evidence

ORD record
ord-7bc8e359fe674399b84a80905712619d
Source dataset
uspto-grants-1992_10
Patent number
US05155113

Reaction notes

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