Reaction #6873

Reaction equation

Trimethylsilyl triflate

mixture 3

5-O-Benzoyl-4-C-benzoyloxymethyl-3-O-benzyl-1,2-di-O-acetyl-D-glucofuranose

thymine

sodium hydrogen carbonate

N,O-bis(trimethylsilyl)acetamide

→

nucleoside

Yield 85.0%

1-(2-O-Acetyl-5-O-benzoyl-4-C-benzoyloxymethyl-3-O-benzyl-β-D-xylofuranosyl)thymine

Yield 85.0%

Solvents

acetonitrile

Conditions

Workup

1. 1
   Temperaturecooled to 0° C
2. 2
   Temperaturethe mixture was subsequently heated for 22 h
3. 3
   Temperatureunder reflux
4. 4
   TemperatureAfter cooling to room temperature
5. 5
   Extractionextraction
6. 6
   WashThe combined organic phase was washed with saturated aqueous solutions of sodium hydrogen carbonate (30 cm3×3) and brine (50 cm3×3)
7. 7
   Dryingdried (Na2SO4)
8. 8
   Concentrationconcentrated under reduced pressure
9. 9
   OtherThe residue was purified by silica gel column chromatography

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.

Source