Methane → HCID 131719122, compound

HRID 2399365Notes

Reaction equation

HRID 2399365 reaction equation
[N:1]([C@:4]1([CH2:19][OH:20])[O:8][C@@H:7]([N:9]2[CH:17]=[C:15]([CH3:16])[C:13](=[O:14])[NH:12][C:10]2=[O:11])[CH2:6][C@@H:5]1[OH:18])=[N+:2]=[N-:3].P(Cl)(Cl)([O:23][P:24](Cl)(Cl)=[O:25])=O.C(=O)(O)[O-:31].[Na+:34].C>C(OCC)(=O)C>[Na+:34].[Na+:34].[P:24]([O:20][CH2:19][C@@:4]1([N:1]=[N+:2]=[N-:3])[O:8][C@@H:7]([N:9]2[CH:17]=[C:15]([CH3:16])[C:13](=[O:14])[NH:12][C:10]2=[O:11])[CH2:6][C@@H:5]1[OH:18])([O-:23])([O-:31])=[O:25]

Participants

6

Reactant 4

HCID 297MethaneHCID 722964'-AzidothymidineHCID 516892Sodium BicarbonateHCID 4432411Diphosphoryl tetrachloride

Product 1

HCID 131719122HCID 131719122, compound

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a suspension of 4'-azidothymidine (0.20 g, 0.71 mM) in ethyl acetate (12 mL) cooled to 0° C. was added pyrophosphoryl chloride (0.5 mL, 3.7 mM). After stirring for 4 hours at 0° C., the solution was neutralized (pH 6 to 7) by the addition of saturated aqueous sodium bicarbonate. The organic phase was discarded, and the aqueous phase was stirred for 20 minutes with activated, 14-60 mesh, charcoal. The charcoal mixture was filtered and the charcoal rinsed with water (200 mL). All filtrates and rinsings were discarded. The charcoal was next washed with 50% aqueous ethanol containing 5% ammonium hydroxide (250 mL). These washings were concentrated in vacuo to about 5 mL and applied onto a 3×23 cm column of DEAE Sephadex (carbonate form). The column was eluted with a linear gradient consisting of 1 L of water and 1 L of 0.5M triethylammonium bicarbonate (pH 7). Pure product was collected and the solvent removed by evaporation. The residue was co-evaporated repeatedly with water, then dissolved in methanol (0.5 mL). The addition of 0.45M sodium perchlorate in acetone (2 mL) to this solution caused the title compound to precipitate out. Filtering off the solid and drying under vacuum left 55 mg of 4'-azidothymidine 5'-monophosphate disodium salt (mp 185° C., decomposition).

Workup

  1. filtrationThe charcoal mixture was filtered
  2. washthe charcoal rinsed with water (200 mL)
  3. washThe charcoal was next washed with 50% aqueous ethanol containing 5% ammonium hydroxide (250 mL)
  4. concentrationThese washings were concentrated in vacuo to about 5 mL
  5. washThe column was eluted with a linear gradient
  6. customPure product was collected
  7. customthe solvent removed by evaporation
  8. dissolutiondissolved in methanol (0.5 mL)
  9. additionThe addition of 0.45M sodium perchlorate in acetone (2 mL) to this solution
  10. customto precipitate out
  11. filtrationFiltering off the solid
  12. customdrying under vacuum
  13. waitleft 55 mg of 4'-azidothymidine 5'-monophosphate disodium salt (mp 185° C., decomposition)

Sources & evidence

ORD record
ord-a828022d765e4298bd370bb5d949bda9
Source dataset
uspto-grants-1995_09
Patent number
US05449664

Reaction notes

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