2-Chloropyridine → HCID 18646874, compound

HRID 728201Notes

Reaction equation

HRID 728201 reaction equation
[H-].[Na+].[F:3][C:4]1[C:5](=[O:38])[NH:6][C:7](=[O:37])[N:8]([CH:36]=1)[C@@H:9]1[O:35][C@H:13]([CH2:14][O:15]C(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[C@@H:11]([OH:12])[CH2:10]1.Cl[C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][N:41]=1>CS(C)=O>[F:3][C:4]1[C:5](=[O:38])[NH:6][C:7](=[O:37])[N:8]([CH:36]=1)[C@@H:9]1[O:35][C@H:13]([CH2:14][OH:15])[C@@H:11]([O:12][C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][N:41]=2)[CH2:10]1

Participants

5

Reactant 3

HCID 79772-ChloropyridineHCID 24758Sodium hydrideHCID 108387042'-deoxy-5'-O-trityl-5-fluorouridine

Product 1

HCID 18646874HCID 18646874, compoundYield 80%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

A 0.30 g quantity of sodium hydride (60%, dispersion in mineral oil) was added to a solution of 2.00 g of 2'-deoxy-5-fluoro-5'-O-trityluridine in 10 ml of dimethyl sulfoxide. The mixture was stirred at room temperature for 30 minutes. To the mixture was added 0.46 ml of 2-chloropyridine. Then the mixture was stirred at 80° C. for 3 hours. The solvent was distilled off and the residue was dissolved in 50 ml of ethyl acetate and 30 ml of water. The solution was made into a weak acidic solution by addition of 6N-hydrochloric acid. The ethyl acetate layer was separated, washed with water and concentrated. The residue was dissolved with heating in 20 ml of 80% acetic acid. The solution was left to stand at 80° C. for 1 hour and concentrated. The residue was dissolved in 50 ml of ethyl acetate, and the solution was washed with water, dried on anhydrous sodium sulfate and concentrated. The residue was purified by silica gel column chromatography using 1% methanol-chloroform as an eluent, giving 1.06 g of 2'-deoxy-5-fluoro-3'-O-(2-pyridyl)uridine in a yield of 80%.

Workup

  1. stirringThen the mixture was stirred at 80° C. for 3 hours
  2. distillationThe solvent was distilled off
  3. dissolutionthe residue was dissolved in 50 ml of ethyl acetate
  4. additionThe solution was made into a weak acidic solution by addition of 6N-hydrochloric acid
  5. customThe ethyl acetate layer was separated
  6. washwashed with water
  7. concentrationconcentrated
  8. dissolutionThe residue was dissolved
  9. temperaturewith heating in 20 ml of 80% acetic acid
  10. waitThe solution was left
  11. waitto stand at 80° C. for 1 hour
  12. concentrationconcentrated
  13. dissolutionThe residue was dissolved in 50 ml of ethyl acetate
  14. washthe solution was washed with water
  15. dry with materialdried on anhydrous sodium sulfate
  16. concentrationconcentrated
  17. customThe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-fad349548b9d4b4ca72d1e5611fdb2e8
Source dataset
uspto-grants-1991_09
Patent number
US05047521

Reaction notes

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