Potassium Hydroxide → 2'-deoxy-5-fluoro-3'-O-(4-carboxybenzyl)uridine

HRID 466101

Reaction equation

HRID 466101 reaction equation
[OH-].[K+].C[O:4][C:5]([C:7]1[CH:14]=[CH:13][C:10]([CH2:11]Br)=[CH:9][CH:8]=1)=[O:6].[F:15][C:16]1[C:17](=[O:50])[NH:18][C:19](=[O:49])[N:20]([CH:48]=1)[C@@H:21]1[O:47][C@H:25]([CH2:26][O:27]C(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[C@@H:23]([OH:24])[CH2:22]1>O1CCOCC1>[F:15][C:16]1[C:17](=[O:50])[NH:18][C:19](=[O:49])[N:20]([CH:48]=1)[C@@H:21]1[O:47][C@H:25]([CH2:26][OH:27])[C@@H:23]([O:24][CH2:11][C:10]2[CH:13]=[CH:14][C:7]([C:5]([OH:4])=[O:6])=[CH:8][CH:9]=2)[CH2:22]1

Participants

5

Reactant 3

HCID 14797Potassium HydroxideHCID 256687Methyl 4-(bromomethyl)benzoateHCID 108387042'-deoxy-5'-O-trityl-5-fluorouridine

Product 1

HCID 140495662'-deoxy-5-fluoro-3'-O-(4-carboxybenzyl)uridineYield 28%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

Potassium hydroxide (4.30 g) and 1.70 g of 4-methoxycarbonylbenzyl bromide were added to a solution of 3.00 g of 2'-deoxy-5-fluoro-5'-O-trityluridine in 200 ml of dioxane. The mixture was stirred at room temperature for a day. The reaction mixture was concentrated under a reduced pressure. To the concentrate was added 200 ml of water and the mixture was stirred at room temperature for 15 minutes. The reaction mixture was rendered acidic with acetic acid, and extracted with ethyl acetate. The organic layer was dried over magnesium sulfate and concentrated under a reduced pressure. The concentrate was dissolved in 50 ml of a 80% aqueous solution of acetic acid. The solution was heated to 100° C. for 2 hours. The solvent was distilled off and the residue was applied to silica gel column chromatography using 3% methanol-chloroform as an eluent, affording 650 mg of the title compound in a yield of 28%.

Workup

  1. concentrationThe reaction mixture was concentrated under a reduced pressure
  2. additionTo the concentrate was added 200 ml of water
  3. stirringthe mixture was stirred at room temperature for 15 minutes
  4. extractionextracted with ethyl acetate
  5. dry with materialThe organic layer was dried over magnesium sulfate
  6. concentrationconcentrated under a reduced pressure
  7. dissolutionThe concentrate was dissolved in 50 ml of a 80% aqueous solution of acetic acid
  8. temperatureThe solution was heated to 100° C. for 2 hours
  9. distillationThe solvent was distilled off

Sources & evidence

ORD record
ord-738dafe8891c4c28bc4232aa6476ea6b
Source dataset
uspto-grants-1992_10
Patent number
US05155113

Linked notes

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