Thymidine → 5'-O-tert-Butyldimethylsilylthymidine

HRID 55551

Reaction equation

HRID 55551 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.C(N(CC)CC)C.[C:25]([Si:29]([CH3:32])([CH3:31])Cl)([CH3:28])([CH3:27])[CH3:26]>CN(C)C=O.C(OCC)(=O)C>[Si:29]([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:25]([CH3:28])([CH3:27])[CH3:26])([CH3:32])[CH3:31]

Participants

6

Reactant 3

HCID 5789ThymidineHCID 8471TriethylamineHCID 28928tert-Butyldimethylsilyl chloride

Product 1

HCID 102512595'-O-tert-ButyldimethylsilylthymidineYield 88.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

5'-O-tert-Butyldimethylsilylthymidine (Compound 2, Table I) was prepared by dissolving thymidine (25 g, 0.10 mole), 4-N,N-dimethylaminopyridine (3.15 g, 0.026 mole) and triethylamine (13.5 g, 18.6 ml, 0.13 mole) in 200 ml of dry N,N-dimethylformamide under a stream of argon. 19.4 g (0.13 mol) tert-butyldimethylchlorosilane was added to the dissolved mixture, with the entire mixture then being stirred for six hours before evaporation of the solvent. The resulting gum was dissolved in 30 ml ethyl acetate and the solution extracted with 10 ml saturated sodium bicarbonate solution, 30 ml water and 30 ml brine. Following drying of the organic layer, the residue was purified by flash chromatography using dichloromethane/ethanol (50/1) as eluent. Evaporation of the product-containing fractions yielded 31.5 g of the desired 5'-O-tert-butyldimethylsilylthymidine as a white foam (86% yield).

Workup

  1. custom5'-O-tert-Butyldimethylsilylthymidine (Compound 2, Table I) was prepared
  2. extractionthe solution extracted with 10 ml saturated sodium bicarbonate solution, 30 ml water and 30 ml brine
  3. customFollowing drying of the organic layer
  4. customthe residue was purified by flash chromatography
  5. customEvaporation of the product-containing fractions

Sources & evidence

ORD record
ord-d4b5a0253f064b57881e8da5d1fae4d0
Source dataset
uspto-grants-1997_04
Patent number
US05625050

Linked notes

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