Thymine → 1(2-O-Acetyl5-O-benzoyl-4-C-benzoyloxymethyl-3-O-benzyl-beta-D-xylofuranosyl)thymine

HRID 6777

Reaction equation

HRID 6777 reaction equation
[C:1]([O:9][C@H:10](CO)[C@@:11]1([CH2:32][O:33][C:34](=[O:41])[C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)[O:19][CH:14](OC(=O)C)[C@H:13]([O:20][C:21](=[O:23])[CH3:22])[C@H:12]1[O:24][CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH:44]1[CH:52]=[C:50]([CH3:51])[C:48](=[O:49])[NH:47][C:45]1=[O:46].C/C(/O[Si](C)(C)C)=N\[Si](C)(C)C.O([Si](C)(C)C)S(C(F)(F)F)(=O)=O.C(=O)([O-])O.[Na+]>C(#N)C>[C:21]([O:20][C@@H:13]1[C@@H:12]([O:24][CH2:25][C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=2)[C:11]([CH2:32][O:33][C:34](=[O:41])[C:35]2[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=2)([CH2:10][O:9][C:1](=[O:8])[C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)[O:19][C@H:14]1[N:44]1[CH:52]=[C:50]([CH3:51])[C:48](=[O:49])[NH:47][C:45]1=[O:46])(=[O:23])[CH3:22]

Participants

7

Reactant 5

HCID 1135ThymineHCID 65367Trimethylsilyl triflateHCID 516892Sodium BicarbonateHCID 6913588N,O-bis(trimethylsilyl)acetamideHCID 235791165-O-Benzoyl-4-C-Benzoyloxymethyl-3-O-Benzyl-1,2-Di-O-Acetyl-D-Glucofuranose

Product 1

HCID 107940411(2-O-Acetyl5-O-benzoyl-4-C-benzoyloxymethyl-3-O-benzyl-beta-D-xylofuranosyl)thymineYield 85%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
60 °C

Procedure

To a stirred suspension of the anomeric mixture 3 (7.26 g, 0.013 mol) and thymine (3.25 g, 0.028 mol) in anhydrous acetonitrile (80 cm3) was added N,O-bis(trimethylsilyl)acetamide (19.1 cm3, 0.077 mol). The reaction mixture was stirred at 60° C. for 1 h and then cooled to 0° C. Trimethylsilyl triflate (4.1 cm3, 0.023 mol) was added drop-wise during 10 min and the mixture was subsequently heated for 22 h under reflux. After cooling to room temperature, a saturated aqueous solution of sodium hydrogen carbonate (30 cm3) was added and extraction was performed using dichloromethane (100 cm3×3). The combined organic phase was washed with saturated aqueous solutions of sodium hydrogen carbonate (30 cm3×3) and brine (50 cm3×3), dried (Na2SO4) and concentrated under reduced pressure. The residue was purified by silica gel column chromatography using dichloromethane/methanol (0.5–2.0% methanol, v/v) as eluent to give nucleoside 4 (6.88 g, 85%) as a white solid material after evaporation of the solvents under reduced pressure.

Workup

  1. temperaturecooled to 0° C
  2. temperaturethe mixture was subsequently heated for 22 h
  3. temperatureunder reflux
  4. temperatureAfter cooling to room temperature
  5. extractionextraction
  6. washThe combined organic phase was washed with saturated aqueous solutions of sodium hydrogen carbonate (30 cm3×3) and brine (50 cm3×3)
  7. dry with materialdried (Na2SO4)
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-ed8ebcb207f34f5b8625d6d6eb29354b
Source dataset
uspto-grants-2006_08
Patent number
US07084125B2

Linked notes

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