Reaction #554618

Reaction equation

cyclohexene

( 5a )

N6-Benzoyl-5′-O-tert-butyldimethylsilyl-2′-deoxyadenosine

5a

N6-Benzoyl-5′-O-tert-butyldimethylsilyl-2′-deoxyadenosine

NH4F

NaN3

N6-benzoyl-3′-O-(methylthiomethyl)-5′-O-(tert-butyldimethylsilyl)-2′-deoxyadenosine

→

9a

Yield 48.1%

N6-benzoyl-3′-O-(azidomethyl)-2′-deoxyadenosine

Yield 48.1%

Solvents

CH2Cl2

Conditions

Workup

1. 1
   OtherThen solvent was removed by rotary evaporation
2. 2
   workup.DISSOLUTIONThen dissolved in 5 mL dry DMF
3. 3
   OtherThen the reaction mixture was partitioned in H2O/CH2Cl2
4. 4
   Dryingthe combined organic part was dried over Na2SO4
5. 5
   Concentrationconcentrated by rotary evaporation
6. 6
   workup.DISSOLUTIONThe crude sample was then dissolved in 5 mL MeOH
7. 7
   OtherThen MeOH was removed by rotary evaporation
8. 8
   OtherAfter partitioning in H2O/EtOAc
9. 9
   Dryingthe combined organic part was dried over Na2SO4
10. 10
    Concentrationconcentrated
11. 11
    Otherpurified by silica gel column chromatography (100% EtOAc to 98:2, EtOAc/MeOH)

Procedure

To 0.4 g N6-benzoyl-3′-O-(methylthiomethyl)-5′-O-(tert-butyldimethylsilyl)-2′-deoxyadenosine (0.76 mmol) dissolved in 7 mL dry CH2Cl2 was treated with 0.4 mL cyclohexene and 155 μL SO2Cl2 (1.91 mmol) at 0° C. for 2 h. During this time the starting material completely converted to 7a which was shown by disappearance of the starting material and appearance of 3′-OH analog (5a) in TLC (EtOAC:Hex/7:3, Rf˜0.3; the 3-CH2Cl (7a) could not detected in TLC due to decomposition in TLC plate to 5a). Then solvent was removed by rotary evaporation and kept about 10 minutes in high vacuum pump. Then dissolved in 5 mL dry DMF and treated with 400 mg NaN3 (6.6 mmol) at room temperature for 3 h. Then the reaction mixture was partitioned in H2O/CH2Cl2, the combined organic part was dried over Na2SO4 and concentrated by rotary evaporation. The crude sample was then dissolved in 5 mL MeOH and treated with 300 mg NH4F (8.1 mmol) more than 38 h. Then MeOH was removed by rotary evaporation. After partitioning in H2O/EtOAc, the combined organic part was dried over Na2SO4, concentrated, and purified by silica gel column chromatography (100% EtOAc to 98:2, EtOAc/MeOH) resulting 150 mg of 9a as white powder (48% yield in three steps). HR-MS: Obs. m/z 411.1530, calcd for C18H19O4N8 411.1529 [M+H]+. 1H-NMR (CDC3): δH 8.84 (brs, 1H), 8.70 (brs, 1H), 8.08 (m, 1H), 7.76-7.54 (m, 5H), 6.47 (t, J=5.6 Hz, 1H), 4.83 (m, 2H), 4.78 (m, 1H), 4.39 (m, 1H), 4.09 (d, J=12.78 Hz, H5′, 1H), 3.88 (d, J=12.78 Hz, H5″, 1H), 3.09 (m, H2′, 1H), and 2.65 (m, H2″, 1H) ppm.

Source