Benzyl Bromide → HCID 54271694, compound

HRID 1379771Notes

Reaction equation

HRID 1379771 reaction equation
COC1C=CC([C:7]([O:22][CH2:23][C@H:24]2[O:28][C@@H:27]([N:29]3[CH:37]=[C:35]([CH3:36])[C:33](=O)[NH:32][C:30]3=[O:31])[CH2:26][C@@H:25]2[OH:38])([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)C2C=CC(OC)=CC=2)=CC=1.[H-].[Na+].C(Br)[C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1.[C:51]([O-:54])(O)=O.[Na+].[H][H]>CN(C=O)C>[CH2:7]([O:22][C@@H:23]1[C@@H:24]([CH2:25][OH:38])[O:28][C@@H:27]([N:29]2[CH:37]=[C:35]([CH3:36])[C:51](=[O:54])[N:32]([CH2:33][C:44]3[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=3)[C:30]2=[O:31])[CH2:26]1)[C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1

Participants

7

Reactant 5

HCID 7498Benzyl BromideHCID 24758Sodium hydrideHCID 1624195'-O-(4,4'-Dimethoxytrityl)thymidineHCID 516892Sodium BicarbonateHCID 178418361HCID 178418361, compound

Product 1

HCID 54271694HCID 54271694, compoundYield 88.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 2.18 g of 5'-O-(4,4'-dimethoxytrityl)-thymidine (4.00 mmol) in 52 mL of dry DMF was carefully added 2.00 g of a 60% oil dispersion of NaH. The reaction was stirred at room temperature for 5 min. To the mixture was added 4.77 mL (40.1 mmol, 10.0 equiv.) of benzyl bromide dropwise, over several minutes. After 1 h, the reaction was cooled on an ice-water bath. Then, 12 mL of sat. aq. NaHCO3 was carefully added (vigorous hydrogen gas evolution) dropwise, over several minutes. The mixture was stirred for 10 min, and then concentrated. The residue was then stirred in 100 mL of 80% aq. HOAc at room temperature for 1.5 h, and then concentrated. The crude residue was partitioned between CH2 Cl2 and H2O, shaken, and separated. The organic layer was washed with sat. aq. NaHCO3, H2O, and then dried. The crude product was purified by flash chromatography on a 50 mm column using two column volumes of CH2Cl2, two column volumes of 1% MeOH in CH2Cl2, and then 2.5% MeOH in CH2Cl2 as eluents. This afforded 1.49 g of product (88.2% yield) as a colorless solid.

Workup

  1. waitover several minutes
  2. waitAfter 1 h
  3. temperaturethe reaction was cooled on an ice-water bath
  4. waitover several minutes
  5. stirringThe mixture was stirred for 10 min
  6. concentrationconcentrated
  7. stirringThe residue was then stirred in 100 mL of 80% aq. HOAc at room temperature for 1.5 h
  8. concentrationconcentrated
  9. customThe crude residue was partitioned between CH2 Cl2 and H2O
  10. stirringshaken
  11. customseparated
  12. washThe organic layer was washed with sat. aq. NaHCO3, H2O
  13. customdried
  14. customThe crude product was purified by flash chromatography on a 50 mm column

Sources & evidence

ORD record
ord-dece5bcf402a407dbeb7679f4104d4e6
Source dataset
uspto-grants-1997_09
Patent number
US05672697

Reaction notes

Loading…