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

HRID 1724623

반응식

HRID 1724623 반응식
[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

참가 물질

8

반응물 4

HCID 8857Ethyl AcetateHCID 127902-FluoroadenineHCID 6097028Ammonium Sulfate2회HCID 228832071-O-acetyl-2,3,5-tri-O-benzoyl-L-lyxofuranose

생성물 1

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

시약·촉매·용매 3

HCID 6342Acetonitrile용매HCID 6344Dichloromethane용매HCID 13838Hexamethyldisilazane용매

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-b577581e6318495c851c22118e4bed18
출처 데이터셋
uspto-grants-2009_02
특허 번호
US07488598B2

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