Imidazole → 3'-O-(t-butyldimethylsilyl)thymidine

HRID 2253920Notes

Reaction equation

HRID 2253920 reaction equation
[C@@H:1]1([N:9]2[CH:17]=[C:15]([CH3:16])[C:13](=[O:14])[NH:12][C:10]2=[O:11])[O:8][C@H:5]([CH2:6][OH:7])[C@@H:3]([OH:4])[CH2:2]1.C1(C(Cl)(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CN(C1C=CC=CN=1)C.N1C=CN=C1.[Si:52](Cl)([C:55]([CH3:58])([CH3:57])[CH3:56])([CH3:54])[CH3:53]>N1C=CC=CC=1>[Si:52]([O:4][C@@H:3]1[C@@H:5]([CH2:6][OH:7])[O:8][C@@H:1]([N:9]2[CH:17]=[C:15]([CH3:16])[C:13](=[O:14])[NH:12][C:10]2=[O:11])[CH2:2]1)([C:55]([CH3:58])([CH3:57])[CH3:56])([CH3:54])[CH3:53]

Participants

7

Reactant 5

HCID 795ImidazoleHCID 5789ThymidineHCID 6456Trityl chlorideHCID 218852-DimethylaminopyridineHCID 28928tert-Butyldimethylsilyl chloride

Product 1

HCID 4538443'-O-(t-butyldimethylsilyl)thymidineYield 71%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of thymidine (10.00 g, 41 mmol) in pyridine (50 ml) was added triphenylmethyl chloride (13.81 g, 50 mmol) and dimethylaminopyridine (0.4 g, 3.0 mmol). The mixture was allowed to stir at 80° C. for 30 min. The pyridine was removed under reduced pressure and the residue dissolved in DMF (80 ml). Imidazole (6.14 g, 90 mmol) and t-butyldimethylsilyl chloride (6.18 g, 41 mmol) were added, and the mixture was allowed to stir overnight at room temperature. The DMF was removed under reduced pressure, and the residue was dissolved in 80% aqueous acetic acid (60 ml). The mixture was allowed to reflux for 30 min, cooled, and neutralized with NaOH. The mixture was lyophilized, and the residue was purified by chromatography (1:1 EtOAc: hexanes) to give 21 as a white solid (10.35 g, 71%): mp 60° C. (softens), 90° C. (melts); Rf 0.69 (1:9 MeOH:CH2Cl2); 1H NMR (CDCl3) 7.33(m, 1H), 6.13(t, 1H, J=6.75 Hz), 4.48(m, 1H), 3.90(m, 2H), 3.74(m, 1H), 2.32(m, 1H), 2.22(m, 1H), 1.89(s, 3H), 0.88(s, 9H), 0.07(s, 6H)ppm.

Workup

  1. customThe pyridine was removed under reduced pressure
  2. dissolutionthe residue dissolved in DMF (80 ml)
  3. stirringto stir overnight at room temperature
  4. customThe DMF was removed under reduced pressure
  5. dissolutionthe residue was dissolved in 80% aqueous acetic acid (60 ml)
  6. temperatureto reflux for 30 min
  7. temperaturecooled
  8. customthe residue was purified by chromatography (1:1 EtOAc: hexanes)

Sources & evidence

ORD record
ord-d096824b9d4a462b837191539c61221f
Source dataset
uspto-grants-1993_08
Patent number
US05233031

Reaction notes

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