Acetic Anhydride → HCID 22859304, compound

HRID 1440005Notes

Reaction equation

HRID 1440005 reaction equation
[F:1][C@@H:2]1[C@@H:6]([CH2:7][OH:8])[O:5][C@@H:4]([N:9]2[CH:16]=[CH:15][C:13](=O)[NH:12][C:10]2=[O:11])[CH2:3]1.[C:17]([O:20]C(=O)C)(=O)[CH3:18].P12(SP3(SP(SP(S3)(S1)=S)(=S)S2)=S)=[S:25]>N1C=CC=CC=1>[C:17]([O:8][CH2:7][C@H:6]1[O:5][C@@H:4]([N:9]2[CH:16]=[CH:15][C:13](=[S:25])[NH:12][C:10]2=[O:11])[CH2:3][C@@H:2]1[F:1])(=[O:20])[CH3:18]

Participants

5

Reactant 3

HCID 7918Acetic AnhydrideHCID 14817Phosphorus sulfide (P2S5)2×HCID 1624502',3'-Dideoxy-3'-fluorouridine

Product 1

HCID 22859304HCID 22859304, compound

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent2×

Procedure

1-(2,3-Dideoxy-3-fluoro-β-D-ribofuranosyl)-uracil (1.3 mmoles) is dissolved in 45 mL of pyridine and treated with 1.1 mL of acetic anhydride. The reaction mixture is allowed to stand overnight at room temperature. The solution is concentrated, the residue dissolved in toluene and evaporated to dryness once more. The process is repeated several times. The residue, finally obtained, is dissolved in 80 mL of pyridine, mixed with 3.9 mmoles of phosphorus pentasulfide and refluxed for 6 hours. After this reaction time, a further 1.3 mmoles of phosphorus pentasulfide are added (J. J. Fox et al., J. Am. Chem. Soc. 1959, 81, 178; G. Kowollik et al., J. Prakt. Chem. 1973, 315, 895) and the mixture is refluxed for 6 hours. The reaction mixture is allowed to cool and the liquid portion is separated is separated from the remainder and evaporated to dryness under vacuum. The resulting residue is purified by column chromatography on a silicage sold by Merck, Darmstadt under the trade name Kieselgel 40, with chloroform as eluting agent. 1-(5-O-Acetyl-2,3-dideoxy-3-fluoro-β-D-ribofuranosyl)-4-thiouracil is isolated from the appropriate fractions and, after recrystallization from 90% ethanol, is obtained in a yield of 97 mg and has a melting point of 140°-140.5° C. This compound (15 mg, 0.06 mmoles) is dissolved in 2 mL of methanol and mixed at 0'C with 2 mL of ammonia-saturated methanol. After 24 hours, the solution is evaporated to dryness. The compound is obtained as a glass.

Workup

  1. concentrationThe solution is concentrated
  2. dissolutionthe residue dissolved in toluene
  3. customevaporated to dryness once more
  4. customThe residue, finally obtained
  5. temperaturerefluxed for 6 hours
  6. temperaturethe mixture is refluxed for 6 hours
  7. temperatureto cool
  8. customthe liquid portion is separated
  9. customis separated from the remainder
  10. customevaporated to dryness under vacuum
  11. customThe resulting residue is purified by column chromatography on a silicage
  12. washas eluting agent

Sources & evidence

ORD record
ord-836f1cf63a104866b4fc5b32be1a6408
Source dataset
uspto-grants-1996_03
Patent number
US05496935

Reaction notes

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