Calcium Carbonate → 2'Fluoro-2'-deoxyuridine

HRID 1385539Notes

Reaction equation

HRID 1385539 reaction equation
[CH:1]1[C:15](=[O:16])[N:14]=[C:13]2[N:3]([C@@H:4]3[O:8][C@H:7]([CH2:9][OH:10])[C@@H:6]([OH:11])[C@@H:5]3[O:12]2)[CH:2]=1.C1C=CN=CC=1.[FH:23].C([O-])([O-])=O.[Ca+2]>O1CCOCC1>[F:23][C@@H:5]1[C@H:6]([OH:11])[C@@H:7]([CH2:9][OH:10])[O:8][C@H:4]1[N:3]1[CH:2]=[CH:1][C:15](=[O:16])[NH:14][C:13]1=[O:12]

Participants

5

Reactant 3

HCID 10112Calcium CarbonateHCID 64774Pyridine, hydrofluoride (1:1)HCID 8061382,2'-Anhydrouridine

Product 1

HCID 1508512'Fluoro-2'-deoxyuridineYield 79%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

The title compound is prepared via a modification of a literature procedure, J. Fox, et al., J. Org. Chem., Vol. 29, pp. 558-564 (1964). Thus, 2,2′-cyclouridine (5.65 g, 25 mmol) is treated with a solution of 70% hydrogen fluoride/pyridine (65 mL) in anhydrous dioxane (500 mL) at 120° C. in a sealed steel vessel for twenty hours. The reaction mixture is cooled to ice temperature, poured into ice (400 mL), and the pH is adjusted to 7 by addition of solid CaCO3. After the solvent is evaporated in vacuo (1 torr), the residue is dissolved in methanol, adsorbed onto silica gel, and purified by column chromatography using silica and ethyl acetatemethanol (v/v, 20:1) as eluent to give 2′-deoxy-2′-fluoro-uridine as a white solid (4.81 g, 79%). The 5′-DMT and 3′-cyanoethoxy-diisopropyl phosphoramidite derivatized nucleoside are obtained in accordance with the procedures of examples 65 and 66.

Workup

  1. temperatureThe reaction mixture is cooled to ice temperature
  2. customAfter the solvent is evaporated in vacuo (1 torr)
  3. dissolutionthe residue is dissolved in methanol
  4. custompurified by column chromatography

Sources & evidence

ORD record
ord-0518e93b92d34a17aa09b4673cdd1987
Source dataset
uspto-grants-2001_07
Patent number
US06262241B1

Reaction notes

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