Reaktion #554622

Reaktionsgleichung

NaN3

cyclohexene

12

N2-isobutyryl-O6-diphenylcarbamoyl-3′-O-(methylthiomethyl)-5′-O-(tert-butyldimethylsilyl)-2′-deoxyguanosine

NH4F

→

14

Ausbeute 36.0%

N2-isobutyryl-O6-diphenylcarbamoyl-3′-O-azidomethyl-2′-deoxyguanosine

Ausbeute 36.0%

Lösungsmittel

CH2Cl2

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeThe solvent was then removed by rotary evaporation
2. 2
   Sonstigefurther dried under high vacuum for 10 minutes
3. 3
   workup.DISSOLUTIONThe crude product was then dissolved in 5 mL dry DMF
4. 4
   workup.STIRRINGstirred at room temperature for 3 h
5. 5
   SonstigeReaction mixture
6. 6
   Extraktionpartitioned H2O/CH2Cl2, the combined organic extract
7. 7
   Trocknenwas then dried over Na2SO4
8. 8
   Einengenconcentrated by rotary evaporation
9. 9
   workup.DISSOLUTIONThe crude was then dissolved in 5 mL dry MeOH
10. 10
    SonstigeThen MeOH solvent was removed by rotary evaporation
11. 11
    Sonstigepartitioned (H2O/CH2Cl2)
12. 12
    TrocknenThe combined organic part was dried over Na2SO4
13. 13
    Einengenconcentrated by rotary evaporation
14. 14
    Sonstigepurified by silica gel column chromatography

Vorschrift

To 786 mg 12 (1.1 mmol) dissolved in 8 mL dry CH2Cl2 was treated with 0.56 mL cyclohexene and 180 μL SO2Cl2 (2.2 mmol) at 0° C. and stirred for 1.5 h at the same temperature. The solvent was then removed by rotary evaporation, and further dried under high vacuum for 10 minutes. The crude product was then dissolved in 5 mL dry DMF and reacted with 600 mg NaN3 (10 mmol) at 0° C. and stirred at room temperature for 3 h. Reaction mixture was then partitioned H2O/CH2Cl2, the combined organic extract was then dried over Na2SO4, and concentrated by rotary evaporation. The crude was then dissolved in 5 mL dry MeOH, treated with 500 mg NH4F (13.5 mmol) at room temperature for more than 24 h. Then MeOH solvent was removed by rotary evaporation, and partitioned (H2O/CH2Cl2). The combined organic part was dried over Na2SO4 and concentrated by rotary evaporation and purified by silica gel column chromatography resulting pure product of 14 as white powder (230 mg, ˜36% yield in three steps; hex:EtOAc 1:1 to 1:5, (Rf=˜0.3, Hex:EtOAc/1:4). HR-MS: Obs. m/z 588.2343, calcd for C28H30O6N9 588.2319 [M+H]+. 1H-NMR (DFM-d6): δH 8.64 (brs, 1H), 7.48-7.34 (m, 10H), 6.36 (t, J=7.0 Hz), 4.93 (m, 2H), 4.76 (m, 1H), 4.04 (m, 1H), 3.57 (m, 1H), 3.34 (m, 2H), 2.97 (m, 1H), 2.81 (m, 1H), and 1.10 (m, 6H).

Quelle