Benzaldehyde → 1-[alpha-(2-Acetoxyethoxy)benzyl]-5-fluorouracil

HRID 1649107Notes

Reaction equation

HRID 1649107 reaction equation
[C:1]1([CH:7]2[O:11][CH2:10][CH2:9][O:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH:12](=[O:19])[C:13]1C=CC=CC=1.C[Si]([C:24]1[NH:29][C:28](=[O:30])[N:27]([Si](C)(C)C)[C:26](=[O:35])[C:25]=1[F:36])(C)C.FC1C(=O)NC(=O)NC=1.C(=O)(O)[O-].[Na+]>C(Cl)(Cl)Cl.CO.C(O)CO>[C:12]([O:8][CH2:9][CH2:10][O:11][CH:7]([N:29]1[CH:24]=[C:25]([F:36])[C:26](=[O:35])[NH:27][C:28]1=[O:30])[C:1]1[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1)(=[O:19])[CH3:13]

Participants

9

Reactant 5

HCID 240BenzaldehydeHCID 33855-FluorouracilHCID 702932-Phenyl-1,3-dioxolaneHCID 516892Sodium BicarbonateHCID 68585259HCID 68585259, compound

Product 1

HCID 130571281-[alpha-(2-Acetoxyethoxy)benzyl]-5-fluorouracil

Reagents, catalysts & solvents 3

HCID 174Ethylene GlycolSolventHCID 887MethanolSolventHCID 6212ChloroformSolvent

Procedure

2-Phenyl-1,3-dioxolan (15 g) prepared from benzaldehyde and ethylene glycol was added to bis(trimethylsilyl)-5-fluorouracil prepared as in Example 1 from 5-fluorouracil (10 g). Then a solution of anhydrous stannic chloride (6 ml) in chloroform (15 ml) was added dropwise to the mixture over one hour while stirring under cooling in an ice bath. Following stirring at room temperature for one hour, the reaction mixture was poured into methanol (200 ml) containing sodium bicarbonate (40 g) followed by stirring at room temperature for one hour. The precipitate was removed by filtration and the filtrate was evaporated under reduced pressure to dryness. Acetic anhydride (20 ml) and pyridine (20 ml) were added to the residue and the mixture was left to stand at room temperature for 3 hours. The reaction mixture was poured into ice-water, and the resulting oil was extracted with chloroform (100 ml). The chloroform layer was washed with hydrochloric acid and then with water, and evaporated under reduced pressure to remove the solvent. The residue was purified by column chromatography using silica gel and chloroform as the eluent, and treated with methanol to give 6.3 g of crystalline 1-[α-(2-acetoxyethoxy)benzyl]-5-fluorouracil.

Workup

  1. temperatureunder cooling in an ice bath
  2. stirringFollowing stirring at room temperature for one hour
  3. stirringby stirring at room temperature for one hour
  4. customThe precipitate was removed by filtration
  5. customthe filtrate was evaporated under reduced pressure to dryness
  6. additionAcetic anhydride (20 ml) and pyridine (20 ml) were added to the residue
  7. waitthe mixture was left
  8. additionThe reaction mixture was poured into ice-water
  9. extractionthe resulting oil was extracted with chloroform (100 ml)
  10. washThe chloroform layer was washed with hydrochloric acid
  11. customwith water, and evaporated under reduced pressure
  12. customto remove the solvent
  13. customThe residue was purified by column chromatography
  14. additiontreated with methanol

Sources & evidence

ORD record
ord-19c12731c775461190fc02a0c70c431e
Source dataset
uspto-grants-1983_11
Patent number
US04415573

Reaction notes

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