Allyl bromide → 3'-O-Allyl-5'-O-(tert-butyldimethylsilyl)-5-iodo-2'-deoxycytidine

HRID 1907103Notes

Reaction equation

HRID 1907103 reaction equation
[H-].[Na+].[Si:3]([O:10][CH2:11][C@H:12]1[O:16][C@@H:15]([N:17]2[CH:24]=[C:23]([I:25])[C:21]([NH2:22])=[N:20][C:18]2=[O:19])[CH2:14][C@@H:13]1[OH:26])([C:6]([CH3:9])([CH3:8])[CH3:7])([CH3:5])[CH3:4].[CH2:27](Br)[CH:28]=[CH2:29]>C1COCC1>[CH2:29]([O:26][C@@H:13]1[C@@H:12]([CH2:11][O:10][Si:3]([C:6]([CH3:9])([CH3:7])[CH3:8])([CH3:4])[CH3:5])[O:16][C@@H:15]([N:17]2[CH:24]=[C:23]([I:25])[C:21]([NH2:22])=[N:20][C:18]2=[O:19])[CH2:14]1)[CH:28]=[CH2:27]

Participants

5

Reactant 3

HCID 7841Allyl bromideHCID 24758Sodium hydrideHCID 573524154-Amino-1-((2R,4S,5R)-5-(((tert-butyldimethylsilyl)oxy)methyl)-4-hydroxytetrahydrofuran-2-yl)-5-iodopyrimidin-2(1H)-one

Product 1

HCID 666840933'-O-Allyl-5'-O-(tert-butyldimethylsilyl)-5-iodo-2'-deoxycytidine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of NaH (60%, 113 mg, 2.84 mmol) in THF (26 ml) under N2 atmosphere, was slowly added a solution of the starting nucleoside (39) (669 mg, 1.43 mmol) in THF (6 ml). The mixture was stirred at room temperature for 45 minutes, cooled at 0° C. and allyl bromide (134 μL, 1.58 mmol) was slowly added. After 15 h at room temperature, the solution was cooled to 0° C. and quenched by addition of H2O (5 ml). THF evaporated under reduced pressure and the product extracted into EtOAc (3×25 ml). Combined organic extracts were dried (MgSO4) filtered and the volatiles evaporated under reduced pressure to give a residue that was purified by flash chromatography on silica gel with EtOAc affording the expected 3′-O-allyl product (40) (323 mg, 44%) as a colourless oil, together with some unreacted starting material (170 mg); 1H NMR (d6 DMSO) δ 0.00 (s, 3H, CH3), 0.01 (s, 3H, CH3), 0.79 (s, 9H, 3CH3), 1.84 (ddd, J=13.3, 8.2 and 5.5 Hz, 1H, H-2′), 2.20-2.25 (m, 1H, H-2′), 3.62-3.72 (m, 2H, H-5′), 3.88-3.93 (m, 4H, H-3′,4′, HHC—CH═), 5.1 (dd, J=8.5, 1.7 Hz, 1H, CH═CHH), 5.16 (dd, J=17.2, 1.7 Hz, 1H, CH═CHH), 5.75-5.83 (m, 1H, CH═CHH), 5.94 (dd, J=8.4, 5.6 Hz, 1H, H-1′), 6.53 (br s, 1H, NHH), 7.74 (br s, 1H, NHH), 7.83 (s, 1H, H-6); MS (ES): m/z (%) (M−H) 506 (100%).

Workup

  1. temperaturecooled at 0° C.
  2. waitAfter 15 h at room temperature
  3. temperaturethe solution was cooled to 0° C.
  4. customquenched by addition of H2O (5 ml)
  5. customTHF evaporated under reduced pressure
  6. extractionthe product extracted into EtOAc (3×25 ml)
  7. dry with materialCombined organic extracts were dried (MgSO4)
  8. filtrationfiltered
  9. customthe volatiles evaporated under reduced pressure
  10. customto give a residue that
  11. customwas purified by flash chromatography on silica gel with EtOAc affording the expected 3′-O-allyl product (40) (323 mg, 44%) as a colourless oil

Sources & evidence

ORD record
ord-2d2d2d11c3e94f6a8d45e69364c07c42
Source dataset
uspto-grants-2013_12
Patent number
US08597881B2

Reaction notes

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