Imidazole → 6-O-(4,4'-dimethoxytrityl)-3-O-(2-fluoroethyl)-4-O-(triethylsilyl)-2-deoxy-2-(thymin-1yl)-D-altro-hexitol

HRID 43300

Reaktionsgleichung

Reaktionsgleichung von HRID 43300
[CH3:1][O:2][C:3]1[CH:46]=[CH:45][C:6]([C:7]([O:22][CH2:23][C@@H:24]([OH:44])[C@@H:25]([OH:43])[C@@H:26]([O:39][CH2:40][CH2:41][F:42])[C@H:27]([N:30]2[CH:38]=[C:36]([CH3:37])[C:34](=[O:35])[NH:33][C:31]2=[O:32])[CH2:28][OH:29])([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.N1C=CN=C1.O=P12OP3(OP(OP(O3)(O1)=O)(=O)O2)=O.Cl[Si:67]([CH2:72][CH3:73])([CH2:70][CH3:71])[CH2:68][CH3:69]>CN(C=O)C.CCOC(C)=O>[CH3:15][O:14][C:11]1[CH:12]=[CH:13][C:8]([C:7]([O:22][CH2:23][C@@H:24]([OH:44])[C@@H:25]([O:43][Si:67]([CH2:72][CH3:73])([CH2:70][CH3:71])[CH2:68][CH3:69])[C@@H:26]([O:39][CH2:40][CH2:41][F:42])[C@H:27]([N:30]2[CH:38]=[C:36]([CH3:37])[C:34](=[O:35])[NH:33][C:31]2=[O:32])[CH2:28][OH:29])([C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=2)[C:6]2[CH:45]=[CH:46][C:3]([O:2][CH3:1])=[CH:4][CH:5]=2)=[CH:9][CH:10]=1

Komponenten

7

Edukt 4

HCID 795ImidazoleHCID 13819ChlorotriethylsilaneHCID 14812Phosphorus oxide (P4O10)HCID 866614446-O-(4,4'-dimethoxytrityl)-2-deoxy-2(thymin-1yl]-3-O-(2-fluoroethyl)D-altro-hexitol

Produkt 1

HCID 866614466-O-(4,4'-dimethoxytrityl)-3-O-(2-fluoroethyl)-4-O-(triethylsilyl)-2-deoxy-2-(thymin-1yl)-D-altro-hexitolAusbeute 82,5 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

Compound 6, prepared as per the procedures illustrated in Example 13 (2.50 g, 4.00 mmol) was mixed with imidazole (1.36 g, 20.0 mmol) over P2O5 under reduced pressure. This mixture was dissolved in anhydrous DMF (13 mL) and chloro triethylsilane (1.71 mL, 10 mmol) was added. The mixture was stirred at room temperature for 12 hours. The reaction mixture was diluted in EtOAc (100 mL), washed with sat. NaHCO3 (100 mL) and brine (50 mL) then dried over anhydrous Na2SO4, filtered and evaporated. The residue was purified by silica gel column chromatography (50% EtOAc in hexanes) to yield Compound 8 (2.45 g, 82.5%) as a white foam. MS (ES): m/z 760.2 [M+Na]+.

Aufarbeitung

  1. washwashed with sat. NaHCO3 (100 mL) and brine (50 mL)
  2. dry with materialthen dried over anhydrous Na2SO4
  3. filtrationfiltered
  4. customevaporated
  5. customThe residue was purified by silica gel column chromatography (50% EtOAc in hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-f76691064f6648a099b401fbe0225912
Quelldatensatz
uspto-grants-2013_09
Patentnummer
US08536320B2

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