Triphenylphosphine → 3'-o-Aminothymidine

HRID 1984953

Reaktionsgleichung

Reaktionsgleichung von HRID 1984953
O.NN.C([O:23][CH2:24][C@H:25]1[O:29][C@@H:28]([N:30]2[CH:38]=[C:36]([CH3:37])[C:34](=[O:35])[NH:33][C:31]2=[O:32])[CH2:27][C@@H:26]1[O:39][N:40]1C(=O)C2=CC=CC=C2C1=O)(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>C(O)C.ClCCl.[Cl-].[Zn+2].[Cl-]>[NH2:40][O:39][C@@H:26]1[C@@H:25]([CH2:24][OH:23])[O:29][C@@H:28]([N:30]2[CH:38]=[C:36]([CH3:37])[C:34](=[O:35])[NH:33][C:31]2=[O:32])[CH2:27]1

Komponenten

7

Edukt 3

HCID 11776TriphenylphosphineHCID 24654Hydrazine hydrate (1:1)HCID 68836402HCID 68836402, Verbindung

Produkt 1

HCID 1904883'-o-Aminothymidine

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 3007855ZincchlorideKatalysatorHCID 702EthanolLösungsmittelHCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

Hydrazine monohydrate (7 mL) is added to a suspension of 5′-O-trityl-3′-O-phthalimido-thymidine (2.9 g; ca. 3 mmol nucleoside, contaminated with some Ph3P═O) in ethanol (30 mL), and the solution is heated under reflux for 2 h. The ethanol is removed in vacuo and the resulting mixture is partitioned between CH2Cl2 (100 mL) and aqueous NaCl (50% sat.; 100 mL). The organic phase is separated and concentrated in vacuo to give a colorless foam, which is redissolved in anhydrous dichloromethane (20 mL). A solution of zinc chloride etherate (1 M in Et2O; 30 mL; 30 mmol) is then added. After a few minutes, the product starts to precipitate. After 30 minutes, the solution is diluted with CH2Cl2 (100 mL) and the precipitate removed by filtration. The solids are partitioned between water (20 mL) and CH2Cl2 (20 mL). The aqueous phase is separated and lyophilized. The crude product is purified by reverse phase HPLC(C18, gradient 0-5% acetonitrile in water over 20 minutes) to give 3′-O-amino-thymidine (expected 340 mg; 44% overall) as a colorless foam. 1H-NMR (DMSO-d6; 300 MHz): δ(ppm)=1.77 (d, J=0.7 Hz, 3H); 1.97-2.07 (m, 1H); 2.29 (ddd, J=0.7, 5.9, 13.7 Hz, 1H); 3.50-3.66 (m, 2H); 3.99-4.03 (m, 1H); 4.16-4.20 (m, 1H); 5.08 (t, J=5.1 Hz, 1H); 6.10-6.16 (m, 3H); 7.73 (d, J=1.0 Hz, 1H); 11.27 (br s, 1H). 13C-NMR (DMSO-d6; 75 MHz): a (ppm)=12.3, 35.7, 62.1, 83.7, 83.7, 83.9, 109.5, 136.0, 150.5, 163.7.

Aufarbeitung

  1. temperaturethe solution is heated
  2. temperatureunder reflux for 2 h
  3. customThe ethanol is removed in vacuo
  4. customthe resulting mixture is partitioned between CH2Cl2 (100 mL) and aqueous NaCl (50% sat.; 100 mL)
  5. customThe organic phase is separated
  6. concentrationconcentrated in vacuo
  7. customto give a colorless foam, which
  8. waitAfter a few minutes
  9. customto precipitate
  10. additionthe solution is diluted with CH2Cl2 (100 mL)
  11. customthe precipitate removed by filtration
  12. customThe solids are partitioned between water (20 mL) and CH2Cl2 (20 mL)
  13. customThe aqueous phase is separated
  14. customThe crude product is purified by reverse phase HPLC(C18, gradient 0-5% acetonitrile in water over 20 minutes)

Quellen und Nachweise

ORD-Eintrag
ord-3e5e00fec8dc4dd383d8489fe62cc1fb
Quelldatensatz
uspto-grants-2009_06
Patentnummer
US07544794B1

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