Imidazole → 5'-O-tert-butyldimethylsilyloxy-3'-deoxythymidine

HRID 76959Notes

Reaction equation

HRID 76959 reaction equation
[C@@H:1]1([N:8]2[CH:16]=[C:14]([CH3:15])[C:12](=[O:13])[NH:11][C:9]2=[O:10])[O:7][C@H:4]([CH2:5][OH:6])[CH2:3][CH2:2]1.N1C=CN=C1.[Si:22](Cl)([C:25]([CH3:28])([CH3:27])[CH3:26])([CH3:24])[CH3:23].CN(C=[O:34])C>>[Si:22]([O:34][O:6][CH2:5][C@H:4]1[O:7][C@@H:1]([N:8]2[CH:16]=[C:14]([CH3:15])[C:12](=[O:13])[NH:11][C:9]2=[O:10])[CH2:2][CH2:3]1)([C:25]([CH3:28])([CH3:27])[CH3:26])([CH3:24])[CH3:23]

Participants

5

Reactant 4

HCID 795ImidazoleHCID 6228DimethylformamideHCID 28928tert-Butyldimethylsilyl chlorideHCID 651192',3'-Dideoxythymidine

Product 1

HCID 873648415'-O-tert-butyldimethylsilyloxy-3'-deoxythymidineYield 87%

Procedure

To a stirred solution of 3′-deoxythymidine (2.0 g, 8.84 mmol) in anhydrous DMF (15 mL) were added imidazole (0.90 g, 13.26 mmol) and tert-butyldimethylsilyl chloride (TBDMSCl) (1.73 g, 11.49 mmol) at r.t., followed by stirring for 4 h. After evaporating the solvent, the residue was partitioned between CH2Cl2 and water. The organic layer was dried over Na2SO4 and evaporated to dryness. The organic residue was purified by silica gel column chromatography with MeOH/CH2Cl2 (0-3%) to give the corresponding product (2.60 g, 7.63 mmol, 87%). 1H NMR (CDCl3, 300 MHz) δ 8.80 (br s, 1H, NH), 7.57 (q, 1H, H6, J=1.2 Hz), 6.07 (dd, 1H, H1′, J=4.8 and 6.3 Hz), 4.10-4.18 (m, 1H, H4′), 3.98 (dd, 1H, H5′, J=2.4 and 11.4 Hz), 3.70 (dd, 1H, H5′, J=3.0 and 11.4 Hz), 2.30-2.4 (m, 1H, H2′), 1.93-2.04 (m, 3H, H2′, and 2H3′), 1.91 (d, 9H, 3 CH3), 0.10 (2 s, 6H, 2 CH3).

Workup

  1. customAfter evaporating the solvent
  2. customthe residue was partitioned between CH2Cl2 and water
  3. dry with materialThe organic layer was dried over Na2SO4
  4. customevaporated to dryness
  5. customThe organic residue was purified by silica gel column chromatography with MeOH/CH2Cl2 (0-3%)

Sources & evidence

ORD record
ord-5a67c9f2df974cbbaf4f429c58cc43c4
Source dataset
uspto-grants-2014_09
Patent number
US08835625B2

Reaction notes

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