Imidazole → 5'-O-tert-Butyldimethylsilylthymidine

HRID 1016695Notes

Reaction equation

HRID 1016695 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.N1C=CN=C1.[C:23]([Si:27](Cl)([CH3:29])[CH3:28])([CH3:26])([CH3:25])[CH3:24]>CN(C=O)C>[Si:27]([O:7][CH2:6][C@H:5]1[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][C@@H:3]1[OH:4])([C:23]([CH3:26])([CH3:25])[CH3:24])([CH3:29])[CH3:28]

Participants

5

Reactant 3

HCID 795ImidazoleHCID 5789ThymidineHCID 28928tert-Butyldimethylsilyl chloride

Product 1

HCID 102512595'-O-tert-ButyldimethylsilylthymidineYield 70.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 2.42 g (10 mmol) thymidine in 15 ml DMF was added 1.7 g (25 mmol) imidazole and 1.6 g (10.6 mmol) tert-butyldimethyl silyl chloride. The solution was stirred at room temperature for 3 hours. DMF was then removed in vacuo and the residue was dissolved in 150 ml of ethyl acetate. The solution was washed with water and the organic layer was dried over MgSO4. After removing the solvent, the solid was recrystallized with ethyl acetate/pentane to obtain 2.5 g pure 5′-O-(tert-butyldimethylsilyl) thymidine 1 (70% yield).: m.p. 193-194° C.; 1H NMR (500 MHz, CDCl3) δ9.0 (s, 1H, NH), 7.50 (s, 1H, H-6), 6.36 (dd, J=5.8, 8.1 Hz, 1H, H-1′), 4.44 (m, 1H, H-3′), 4.03 (m, 1H, H-4′), 3.85 (m, 2H, H-5′), 2.66 (d, J=3.8 Hz, 1H, OH), 2.35 (m, 1H, H-2′), 2.07 (m, 1H, H-2′), 1.89 (s, 3H, C═CMe), 0.89 (s, 9H, CMe3), 0.09 (s, 6H, SiMe2); 13C NMR (125 MHz, CDCl3) δ163.8 (C-4), 150.4 (C-2), 135.4 (C-6), 110.9 (C-5), 87.2 (C-4′), 85.0 (C-1′), 72.6 (C-3′), 63.6 (C-5′), 41.1 (C-2′), 25.9 (SiCMe3), 18.3 (SiCMe3), 12.5 (C═CMe), −5.4 (SiMe2), −5.5 (SiMe2).

Workup

  1. customDMF was then removed in vacuo
  2. dissolutionthe residue was dissolved in 150 ml of ethyl acetate
  3. washThe solution was washed with water
  4. dry with materialthe organic layer was dried over MgSO4
  5. customAfter removing the solvent
  6. customthe solid was recrystallized with ethyl acetate/pentane

Sources & evidence

ORD record
ord-a2eb6500a54344268a0fa6cc4025ed9f
Source dataset
uspto-grants-2002_11
Patent number
US06476216B1

Reaction notes

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