Reaction #1994273

Reaction equation

( 3 )

5′-O-(tert-Butydimethylsilyl)-3′-O-methylthiomethyl-5-[3-(2,2,2-trifluoroacetamido)-prop-1-ynyl]-2′-deoxyuridine

cyclohexene

sulfurylchloride

N2

NaN3

→

( 4 )

Yield 37.0%

3′-O-Azidomethyl-5-[3-(2,2,2-trifluoroacetamido)-prop-1-ynyl]-2′-deoxyuridine

Yield 37.0%

Solvents

CH2Cl2

Conditions

Workup

1. 1
   Otherthe full consumption of the nucleoside (3)
2. 2
   OtherThe solvent was evaporated
3. 3
   workup.WAITthe residue was subjected to high vacuum for 20 min
4. 4
   workup.DISSOLUTIONIt was then redissolved in dry DMF (3 ml)
5. 5
   OtherThe reaction was quenched with CH2Cl2
6. 6
   Washthe organic layers were washed with sat aq. NaCl solution
7. 7
   OtherAfter removing the solvent
8. 8
   workup.DISSOLUTIONthe resulting yellow gum was redissolved in THF (2 ml)
9. 9
   workup.ADDITIONtreated with TBAF (1M in THF, 0.5 ml) at room temperature for 30 min
10. 10
    OtherThe solvent was removed
11. 11
    ExtractionThe aqueous layer was extracted three times with CH2Cl2
12. 12
    OtherPurification by chromatography on silica (EtOAc: petroleum ether 1:1 to EtOAc)

Procedure

To a solution of (3) (348 mg, 0.63 mmol) and cyclohexene (0.32 ml, 3.2 mmol) in dry CH2Cl2 (5 ml) at 4° C., sulfurylchloride (1M in CH2Cl2, 0.76 ml, 0.76 mmol) was added drop wise under N2. After 10 min TLC indicated the full consumption of the nucleoside (3). The solvent was evaporated and the residue was subjected to high vacuum for 20 min. It was then redissolved in dry DMF (3 ml) and treated with NaN3 (205 mg, 3.15 mmol). The resulting suspension was stirred under room temperature for 2 h. The reaction was quenched with CH2Cl2 and the organic layers were washed with sat aq. NaCl solution. After removing the solvent, the resulting yellow gum was redissolved in THF (2 ml) and treated with TBAF (1M in THF, 0.5 ml) at room temperature for 30 min. The solvent was removed and the reaction worked up with CH2Cl2 and sat. aq. NaHCO3 solution. The aqueous layer was extracted three times with CH2Cl2. Purification by chromatography on silica (EtOAc: petroleum ether 1:1 to EtOAc) gave (4) (100 mg, 37%) as a pale yellow foam. 1H NMR (d6 DMSO) δ 2.15-2.26 (m, 2H, H-2′), 3.47-3.57 (m, 2H, H-5′), 3.88-3.90 (m, 1H, H-4′), 4.14 (d, J=4.7 Hz, 2H, CH2NH), 4.24-4.27 (m, 1H, H-3′), 4.75 (s, 2H, CH2N3), 5.14 (t, J=5.2 Hz, 1H, OH), 5.96-6.00 (m, 1H, H-1′), 8.10 (s, 1H, H-6), 10.00 (s, 1H, NHCOCF3)), 11.26 (s, 1H, NH).

Source