Triethyl Phosphate → HCID 86625112, compound

HRID 1640035Notes

Reaction equation

HRID 1640035 reaction equation
[N:1]([C@@:4]1([OH:20])[C@@H:8]([CH2:9][OH:10])[O:7][C@@H:6]([N:11]2[CH:19]=[C:17]([CH3:18])[C:15](=[O:16])[NH:14][C:12]2=[O:13])[CH2:5]1)=[N+:2]=[N-:3].[CH2:21]([O:23][P:24](O[CH2:30][CH3:31])([O:26]CC)=[O:25])C.P(Cl)(Cl)(Cl)=O.[OH-].[Na+]>O>[CH2:19]([NH+:11]([CH2:6][CH3:5])[CH2:12][CH3:21])[CH3:17].[P:24]([O:10][CH2:9][C@H:8]1[O:7][C@@H:6]([N:11]2[CH:19]=[C:17]([CH3:18])[C:15](=[O:16])[NH:14][C:12]2=[O:13])[CH2:5][C@:4]1([N:1]=[N+:2]=[N-:3])[OH:20])([O-:26])([O-:25])=[O:23].[CH2:6]([NH+:11]([CH2:30][CH3:31])[CH2:19][CH3:17])[CH3:5]

Participants

6

Reactant 4

HCID 6535Triethyl Phosphate2×HCID 14798Sodium HydroxideHCID 24813Phosphorus oxychlorideHCID 21115113HCID 21115113, compound

Product 1

HCID 86625112HCID 86625112, compoundYield 40%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
2 °C

Procedure

A mixture of 100 mg of 3′-azido-thymidine (0.37 mmol) and 0.5 ml triethylphosphate was gradually added to a mixture of 1 ml triethylphosphate and 100 μl phosphorus oxychloride (1.0 mmol) at 0° C. The mixture was maintained at 0-4° C. for 16 h under stirring. Then 10 ml of ice-cold 5% NaHCO3 in water was added and after stirring at 0° C. for 1 hour, the pH was adjusted to 7.0 with NaOH 1M. After further 12 h under stirring, the mixture was extract with 3×10 ml of diethyl ether to remove triethylphosphate. The water solution was subjected to volume reduction (1 ml) and loaded onto a DEAE-cellulose column. The column was eluted with a linear gradient (0.05-0.4 M) of triethylammonium bicarbonate, pH 7.5. Appropriate fractions were evaporated under vacuum. Methanol was added and evaporated again to remove triethylammonium bicarbonate obtaining 3′-azidothymidine-5′-monophosphate triethylammonium salt as white solid (90 mg, 0.15 mmol, yield=40%).

Workup

  1. stirringafter stirring at 0° C. for 1 hour
  2. stirringAfter further 12 h under stirring
  3. extractionthe mixture was extract with 3×10 ml of diethyl ether
  4. customto remove triethylphosphate
  5. washThe column was eluted with a linear gradient (0.05-0.4 M) of triethylammonium bicarbonate, pH 7.5
  6. customAppropriate fractions were evaporated under vacuum
  7. additionMethanol was added
  8. customevaporated again
  9. customto remove triethylammonium bicarbonate

Sources & evidence

ORD record
ord-3cd337b9b22a4f19ade73b9a5cb2307d
Source dataset
uspto-grants-2012_02
Patent number
US08110676B2

Reaction notes

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