Ethyl Acetate → 2-Fluoro-9-(2,3,5-tri-O-benzoyl-alpha-L-lyxofuranosyl)-9H-purin-6-amine

HRID 1724623

Reaktionsgleichung

Reaktionsgleichung von HRID 1724623
[F:1][C:2]1[N:10]=[C:9]2[C:5]([NH:6][CH:7]=[N:8]2)=[C:4]([NH2:11])[N:3]=1.S([O-])([O-])(=O)=O.[NH4+].[NH4+].C(O[CH:23]1[O:45][C@@H:44]([CH2:46][O:47][C:48](=[O:55])[C:49]2[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=2)[C@@H:34]([O:35][C:36](=[O:43])[C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)[C@H:24]1[O:25][C:26](=[O:33])[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)(=O)C.C(OCC)(=O)C>C[Si](C)(C)N[Si](C)(C)C.C(#N)C.ClCCl>[F:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[C@@H:23]2[O:45][C@@H:44]([CH2:46][O:47][C:48](=[O:55])[C:49]3[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=3)[C@@H:34]([O:35][C:36](=[O:43])[C:37]3[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=3)[C@H:24]2[O:25][C:26](=[O:33])[C:27]2[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=2)=[C:4]([NH2:11])[N:3]=1

Komponenten

8

Edukt 4

HCID 8857Ethyl AcetateHCID 127902-FluoroadenineHCID 6097028Ammonium Sulfate2×HCID 228832071-O-acetyl-2,3,5-tri-O-benzoyl-L-lyxofuranose

Produkt 1

HCID 690770502-Fluoro-9-(2,3,5-tri-O-benzoyl-alpha-L-lyxofuranosyl)-9H-purin-6-amine

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 6342AcetonitrileLösungsmittelHCID 6344DichloromethaneLösungsmittelHCID 13838HexamethyldisilazaneLösungsmittel

Versuchsvorschrift

A suspension of a 2-fluoroadenine (107.8 mg, 0.70 mmol) and ammonium sulfate (5.3 mg) in 1,1,1,3,3,3-hexamethyldisilazane (HMDS) (10 ml) is refluxed under argon for 7 h. More ammonium sulfate (4.6 mg) is added, and reflux is continued for 24 h. After cooling the reaction mixture to room temperature, the HMDS is removed in vacuo, and the residue is co-evaporated with anhydrous toluene (3×3 ml). To this material is added 1-O-acetyl-2,3,5-tri-O-benzoyl-L-lyxofuranose (212 mg, 0.42 mmol) dissolved in anhydrous acetonitrile (7 ml). The resulting suspension is chilled to −10° C. before being treated dropwise over 5 min with 2.1 ml of 1.0 M stannic chloride (SnCl4) in dichloromethane. The now clear reaction solution is warmed to 0° C. over 15 min and then stirred at room temperature. After 3 h, the solution is added dropwise to ice-cold saturated NaHCO3 (100 ml) and stirred 10 min at 5° C. Ethyl acetate (75 ml) is added, and the separated aqueous layer is extracted with more ethyl acetate (2×50 ml). The combined organics are washed with brine (50 ml), dried (MgSO4), and evaporated to a solid. Column chromatography on 20 g silica gel (95:5 chloroform-methanol) gave 1 a as a white solid after ethanol crystallization.

Aufarbeitung

  1. temperatureis refluxed under argon for 7 h
  2. temperaturereflux
  3. customthe HMDS is removed in vacuo
  4. temperatureThe resulting suspension is chilled to −10° C.
  5. temperatureThe now clear reaction solution is warmed to 0° C. over 15 min
  6. waitAfter 3 h
  7. stirringstirred 10 min at 5° C
  8. extractionthe separated aqueous layer is extracted with more ethyl acetate (2×50 ml)
  9. washThe combined organics are washed with brine (50 ml)
  10. dry with materialdried (MgSO4)
  11. customevaporated to a solid
  12. customColumn chromatography on 20 g silica gel (95:5 chloroform-methanol) gave 1 a as a white solid
  13. customafter ethanol crystallization

Quellen und Nachweise

ORD-Eintrag
ord-b577581e6318495c851c22118e4bed18
Quelldatensatz
uspto-grants-2009_02
Patentnummer
US07488598B2

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