Water → 5'-O-(Bis(4-methoxyphenyl)(phenyl)methyl)-2'-deoxy-2'-fluorouridine

HRID 2206357Notes

Reaction equation

HRID 2206357 reaction equation
[F:1][C@@H:2]1[C@H:6]([OH:7])[C@@H:5]([CH2:8][OH:9])[O:4][C@H:3]1[N:10]1[CH:17]=[CH:16][C:14](=[O:15])[NH:13][C:11]1=[O:12].[CH3:18][O:19][C:20]1[CH:41]=[CH:40][C:23]([C:24](Cl)([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[C:25]2[CH:30]=[CH:29][C:28]([O:31][CH3:32])=[CH:27][CH:26]=2)=[CH:22][CH:21]=1.C(OCC)(=O)C.O>N1C=CC=CC=1>[CH3:32][O:31][C:28]1[CH:27]=[CH:26][C:25]([C:24]([O:9][CH2:8][C@H:5]2[O:4][C@@H:3]([N:10]3[CH:17]=[CH:16][C:14](=[O:15])[NH:13][C:11]3=[O:12])[C@H:2]([F:1])[C@@H:6]2[OH:7])([C:33]2[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=2)[C:23]2[CH:40]=[CH:41][C:20]([O:19][CH3:18])=[CH:21][CH:22]=2)=[CH:30][CH:29]=1

Participants

6

Reactant 4

HCID 962WaterHCID 8857Ethyl AcetateHCID 968311,1'-(Chlorophenylmethylene)bis(4-methoxybenzene)HCID 1508512'Fluoro-2'-deoxyuridine

Product 1

HCID 70731865'-O-(Bis(4-methoxyphenyl)(phenyl)methyl)-2'-deoxy-2'-fluorouridineYield 126.7%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

An operation of dissolving 2′-Deoxy-2′-fluorouridine (3.00 g, 12.2 mmol) in dry pyridine, followed by concentration under reduced pressure was repeated 3 times to perform dehydrative azeotropic distillation. Thereafter, under an argon atmosphere, the reaction mixture was dissolved in dry pyridine (120 ml), 4,4′-dimethoxytrityl chloride (4.55 g, 13.4 mmol) was added, and the mixture was stirred at room temperature for 3 hr. The completion of the reaction was confirmed, and ethyl acetate (150 ml) and water (60 ml) were added to the reaction mixture to allow layer separation. The organic layer was washed 3 times with 5% aqueous sodium hydrogen carbonate solution (20 ml), washed with water (20 ml) and saturated brine (20 ml), and the obtained organic layer was dried over sodium sulfate. The solvent in the filtrate was evaporated and the obtained residue was purified by silica gel column chromatography (hexane:ethyl acetate=50:50-0/100 (v/v), containing 1% triethylamine). The object fractions were collected and concentrated to give the title compound (8.48 g, quant).

Workup

  1. distillationazeotropic distillation
  2. dissolutionThereafter, under an argon atmosphere, the reaction mixture was dissolved in dry pyridine (120 ml)
  3. customlayer separation
  4. washThe organic layer was washed 3 times with 5% aqueous sodium hydrogen carbonate solution (20 ml)
  5. washwashed with water (20 ml) and saturated brine (20 ml)
  6. dry with materialthe obtained organic layer was dried over sodium sulfate
  7. customThe solvent in the filtrate was evaporated
  8. customthe obtained residue was purified by silica gel column chromatography (hexane:ethyl acetate=50:50-0/100 (v/v), containing 1% triethylamine)
  9. customThe object fractions were collected
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-26c56df0c31a4b11884ba25efa0dba40
Source dataset
uspto-grants-2016_06
Patent number
US09371353B2

Reaction notes

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