Reaction #1652

Reaction equation

2,5-dimethoxytetrahydrofuran

tin tetrachloride

ammonium sulfate

chlorotrimethylsilane

thymine

→

title compound

1-(5-Methoxytetrahydro-2-furyl) thymine

Solvents

dichloroethane

ethyl acetate

hexamethyldisilazane

Conditions

Workup

1. 1
   OtherThe excess hexamethyldisilazane was removed at reduced pressure
2. 2
   workup.DISSOLUTIONthe residual oil was dissolved in xylene
3. 3
   Otherevaporated in vacuo
4. 4
   Otherto give a colorless viscous oil
5. 5
   TemperatureAfter cooling the solution to -30° C.
6. 6
   Temperatureto warm to -10° C.
7. 7
   FiltrationThe mixture was filtered
8. 8
   Otherthe organic phase was separated
9. 9
   Dryingdried (MgSO4)
10. 10
    OtherThe solvent was removed under reduced pressure
11. 11
    Otherthe residual oil was chromatographed on silica gel

Procedure

To a suspension of thymine (2.5 g, 20 mmol) in hexamethyldisilazane (30 mL) was added ammonium sulfate (50 mg) and chlorotrimethylsilane (0.5 mL) and the mixture was heated at 145° C. for 4 hr under nitrogen. The excess hexamethyldisilazane was removed at reduced pressure, and the residual oil was dissolved in xylene and evaporated in vacuo to give a colorless viscous oil. To this silylated thymine in dichloroethane (40 mL) was added 2,5-dimethoxytetrahydrofuran (7 mL). After cooling the solution to -30° C., tin tetrachloride (2.3 mL) was added dropwise via a syringe under nitrogen. The mixture was allowed to warm to -10° C. and was then poured into ice cold aqueous sodium bicarbonate (100 mL) and ethyl acetate (150 mL). The mixture was filtered and the organic phase was separated and dried (MgSO4). The solvent was removed under reduced pressure and the residual oil was chromatographed on silica gel using CH2Cl2 /5% MeOH as eluent to give the title compound as a cis/trans mixture in a ratio of 1:1 as shown by analytical HPLC and 1H-NMR: yield 3.4 g (75%).

Source