Pyridine → HCID 22881709, compound

HRID 727465Notes

Reaction equation

HRID 727465 reaction equation
[CH3:1][O:2][C:3]1[CH:40]=[CH:39][C:6]([C:7]([O:22][C@@H:23]2[C@@H:27]([CH2:28][OH:29])[O:26][C@@H:25]([N:30]3[CH:38]=[C:36]([CH3:37])[C:34](=[O:35])[NH:33][C:31]3=[O:32])[CH2:24]2)([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[C:8]2[CH:13]=[CH:12][C:11]([O:14][CH3:15])=[CH:10][CH:9]=2)=[CH:5][CH:4]=1.[C@@H]1(N2C=C(C)C(=O)NC2=O)O[C@H](CO)[C@@H:43]([OH:44])C1.C1CCC(N=C=NC2CCCCC2)CC1.N1C=CC=CC=1>CS(C)=O.O>[CH3:1][O:2][C:3]1[CH:40]=[CH:39][C:6]([C:7]([O:22][C@@H:23]2[C@@H:27]([CH:28]([CH:43]=[O:44])[OH:29])[O:26][C@@H:25]([N:30]3[CH:38]=[C:36]([CH3:37])[C:34](=[O:35])[NH:33][C:31]3=[O:32])[CH2:24]2)([C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=2)[C:8]2[CH:13]=[CH:12][C:11]([O:14][CH3:15])=[CH:10][CH:9]=2)=[CH:5][CH:4]=1

Participants

7

Reactant 4

HCID 1049PyridineHCID 5789ThymidineHCID 10868DicyclohexylcarbodiimideHCID 2729833AG-H-03352

Product 1

HCID 22881709HCID 22881709, compoundYield 81%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolvent3×HCID 962WaterSolvent

Conditions

Temperature
5 °C

Procedure

To a stirred, cold solution of 3'-O-(4,4'-dimethoxytrityl)thymidine (prepared from thymidine by the common procedures, 40.4 g, 0.072 mol) in anhydrous DMSO was added a solution of DCC (45.86 g, 0.224 mol) in DMSO (180 ml). The resulting solution was stirred at 5° C. for 5 min. pyridine (2.94 g, 3.0 ml, 0.0371 mol) was added and after stirring for another 5 min. a solution of trifluorocaetic acid (2.11 g, 1.43 ml, 0.0185 mol) in DMSO (2 ml) was added dropwise. The resulting reaction mixture was stirred at 5° C. for 10 min. and at room temperature for 6 h. Water (20 ml) was added dropwise under cooling and the mixture stirred at room temperature for 1 h. Precipitates were filtered and washed with DMSO. The combined DMSO solution was poured onto crashed ice (4 L) with stirring. After standing for 1 h, the precipitates were filtered and washed thoroughly with water. The cake was dissolved in methylene chloride (5 00 ml), and the organic layer separated, dried (Na2SO4), and concentrated. The crude was purified by chromatography on silica (3% methanol in methylene chloride) to give 32.6 g (81%) of 3'-O-(4,4'dimethoxytrityl)-5'-formylthymidine as a colorless powder.

Workup

  1. additionwas added
  2. additionwas added dropwise
  3. customThe resulting reaction mixture
  4. temperatureunder cooling
  5. stirringthe mixture stirred at room temperature for 1 h
  6. customPrecipitates
  7. filtrationwere filtered
  8. washwashed with DMSO
  9. additionThe combined DMSO solution was poured
  10. stirringwith stirring
  11. waitAfter standing for 1 h
  12. filtrationthe precipitates were filtered
  13. washwashed thoroughly with water
  14. dissolutionThe cake was dissolved in methylene chloride (5 00 ml)
  15. customthe organic layer separated
  16. dry with materialdried (Na2SO4)
  17. concentrationconcentrated
  18. customThe crude was purified by chromatography on silica (3% methanol in methylene chloride)

Sources & evidence

ORD record
ord-c61f81fa504a450a8949a92d5cc245ac
Source dataset
uspto-grants-1998_01
Patent number
US05712378

Reaction notes

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