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

HRID 1363686Notes

Reaction equation

HRID 1363686 reaction equation
[Si:1]([O:8][CH2:9][C@H:10]1[O:14][C@@H:13]([N:15]2[CH:22]=[C:21]([I:23])[C:19]([NH2:20])=[N:18][C:16]2=[O:17])[CH2:12][C@@H:11]1[OH:24])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[H-].[Na+].[CH2:27](Br)[CH:28]=[CH2:29].C([O-])(O)=O.[Na+]>C1COCC1>[CH2:29]([O:24][C@@H:11]1[C@@H:10]([CH2:9][O:8][Si:1]([C:4]([CH3:7])([CH3:5])[CH3:6])([CH3:2])[CH3:3])[O:14][C@@H:13]([N:15]2[CH:22]=[C:21]([I:23])[C:19]([NH2:20])=[N:18][C:16]2=[O:17])[CH2:12]1)[CH:28]=[CH2:27]

Participants

6

Reactant 4

HCID 7841Allyl bromideHCID 24758Sodium hydrideHCID 516892Sodium BicarbonateHCID 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'-deoxycytidineYield 47%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of 18 (1.18 g; 2.52 mmol) in anhydrous THF (43 mL), 95% NaH powder (128 mg; 5.07 mmol) was added. The suspension mixture was stirred at room temperature for 45 min. Allyl bromide (240 μL, 2.79 mmol) was then added at 0° C. and the reaction was stirred at room temperature for another 14 h with exclusion of moisture. Saturated aqueous NaHCO3 (10 mL) was added at 0° C. and the reaction mixture was stirred for 10 min. After evaporation, the residue was dissolved in ethyl acetate (150 mL). The solution was then washed with saturated aqueous NaHCO3 and NaCl, and dried over anhydrous Na2SO4. After evaporation, the residue was purified by flash column chromatography using ethyl acetate as the eluent to afford 19 as white solid (601 mg; 47% yield): 1H NMR (400 MHz, CD3OD) δ 8.15 (s, 1H, 6-H), 6.12 (dd, J=5.6, 8.0 Hz, 1H, 1′-H), 4.17 (m, 1H, 4′-H), 4.14 (m, 1H, 3′-H), 3.98-4.10 (m, 2H, CH2CH═CH2), 3.93 (dd, J=2.8, 11.5 Hz, 1H, one of 5′-H), 3.83 (dd, J=2.8, 11.5 Hz, 1H, one of 5′-H), 2.53-2.60 (ddd, J=1.7, 5.6, 13.6 Hz, 1H, one of 2′-H), 1.94-2.02 (ddd, J=5.9, 8.0, 13.6 Hz, 1H, one of 2′-H), 0.94 (s, 9H, C(CH3)3), 0.17 (s, 3H, one of SiCH3), 0.16 (s, 3H, one of SiCH3); 13C NMR (100 MHz, CD3OD) δ 165.4, 156.7, 147.7, 135.5, 117.2, 88.2, 87.0, 80.4, 70.9, 64.8, 57.3, 40.1, 26.7, 19.4, −4.7, −4.9; HRMS (FAB+) calcd for C18H31O4N3SiI (M+H+): 508.1129, found: 568.1123.

Workup

  1. stirringthe reaction was stirred at room temperature for another 14 h with exclusion of moisture
  2. stirringthe reaction mixture was stirred for 10 min
  3. customAfter evaporation
  4. dissolutionthe residue was dissolved in ethyl acetate (150 mL)
  5. washThe solution was then washed with saturated aqueous NaHCO3 and NaCl
  6. dry with materialdried over anhydrous Na2SO4
  7. customAfter evaporation
  8. customthe residue was purified by flash column chromatography

Sources & evidence

ORD record
ord-a44622c7d26841c69feed2c898a03ce9
Source dataset
uspto-grants-2011_02
Patent number
US07883869B2

Reaction notes

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