Sulfuric Acid → HCID 59460451, compound

HRID 1713328Notes

Reaction equation

HRID 1713328 reaction equation
[Si]([O:8][C@@H:9]1[C@H:13]([O:14][Si](C(C)(C)C)(C)C)[C@@H:12]([CH2:22][O:23][Si](C(C)(C)C)(C)C)[O:11][C@H:10]1[N:31]1[C:40]2[N:39]=[CH:38][N:37]=[C:35]([NH2:36])[C:34]=2[N:33]=[C:32]1[NH:41][CH2:42][C:43]1[CH:48]=[CH:47][C:46]([C:49]2[CH:54]=[CH:53][CH:52]=[C:51]([C:55](OC)=[O:56])[CH:50]=2)=[CH:45][CH:44]=1)(C(C)(C)C)(C)C.[H-].[Al+3].[Li+].[H-].[H-].[H-].C(OCC)(=O)C.S(=O)(=O)(O)O>O1CCCC1.O>[OH:56][CH2:55][C:51]1[CH:50]=[C:49]([C:46]2[CH:47]=[CH:48][C:43]([CH2:42][NH:41][C:32]3[N:31]([C:40]4[N:39]=[CH:38][N:37]=[C:35]([NH2:36])[C:34]=4[N:33]=3)[C@@H:10]3[O:11][C@H:12]([CH2:22][OH:23])[C@@H:13]([OH:14])[C@H:9]3[OH:8])=[CH:44][CH:45]=2)[CH:54]=[CH:53][CH:52]=1

Participants

7

Reactant 4

HCID 1118Sulfuric AcidHCID 8857Ethyl AcetateHCID 21226445Aluminium lithium hydride2×HCID 67455411HCID 67455411, compound

Product 1

HCID 59460451HCID 59460451, compoundYield 55.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To an ice-cold solution of 2′,3′,5′-tris-O-(tert-butyldimethylsilyl)-8-(3′-methoxycarbonylbiphenyl-4-ylmethylamino)adenosine (0.224 g) in tetrahydrofuran (2.6 mL) was added lithium aluminum hydride (0.013 g) in several portions, and the resulting mixture was stirred at room temperature for 2 hours. Lithium aluminum hydride (0.006 g) was added and stirring was continued for additional 2 hours. Ethyl acetate (1.0 mL), 0.5 mol/L sulfuric acid (1 mL) and water (9 mL) were added sequentially and the whole was extracted with ethyl acetate (35 mL). The organic layer was washed successively with 0.5 mol/L sulfuric acid/water (1/9, 10 mL×2), saturated aqueous sodium hydrogen carbonate (10 mL) and brine (10 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue (0.173 g) was dissolved in methanol (2.1 mL). Ammonium fluoride (0.468 g) was added, and the resulting mixture was stirred at 60° C. for 21 hours. The reaction mixture was cooled to room temperature. Dichloromethane (10 mL) was added and the insoluble material was filtered out. The filtrate was concentrated under reduced pressure and the residue was purified by column chromatography on aminopropylated silica gel (eluent: dichloromethane/methanol=10/1 to 6/1) to give the title compound (0.070 g).

Workup

  1. stirringstirring
  2. waitwas continued for additional 2 hours
  3. extractionthe whole was extracted with ethyl acetate (35 mL)
  4. washThe organic layer was washed successively with 0.5 mol/L sulfuric acid/water (1/9, 10 mL×2), saturated aqueous sodium hydrogen carbonate (10 mL) and brine (10 mL)
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. dissolutionThe residue (0.173 g) was dissolved in methanol (2.1 mL)
  8. additionAmmonium fluoride (0.468 g) was added
  9. stirringthe resulting mixture was stirred at 60° C. for 21 hours
  10. temperatureThe reaction mixture was cooled to room temperature
  11. additionDichloromethane (10 mL) was added
  12. filtrationthe insoluble material was filtered out
  13. concentrationThe filtrate was concentrated under reduced pressure
  14. customthe residue was purified by column chromatography on aminopropylated silica gel (eluent: dichloromethane/methanol=10/1 to 6/1)

Sources & evidence

ORD record
ord-e187406206924ea69bdfa0086e4b434e
Source dataset
uspto-grants-2010_09
Patent number
US07795236B2

Reaction notes

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