Tetrahydrofuran → Sonedenoson

HRID 1392016Notes

Reaction equation

HRID 1392016 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][O:10][C:11]2[N:12]=[C:13]([NH2:50])[C:14]3[N:15]=[CH:16][N:17]([C:48]=3[N:49]=2)[C@@H:18]2[O:47][C@H:37]([CH2:38][O:39][Si](C(C)(C)C)(C)C)[C@@H:28]([O:29][Si](C(C)(C)C)(C)C)[C@H:19]2[O:20][Si](C(C)(C)C)(C)C)=[CH:4][CH:3]=1.CCCC[N+](CCCC)(CCCC)CCCC.[F-].C1COCC1>CO>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:8][CH2:9][O:10][C:11]2[N:12]=[C:13]([NH2:50])[C:14]3[N:15]=[CH:16][N:17]([C:48]=3[N:49]=2)[C@@H:18]2[O:47][C@H:37]([CH2:38][OH:39])[C@@H:28]([OH:29])[C@H:19]2[OH:20])=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 2724141Tetrabutylammonium FluorideHCID 156063272-[2-(4-Chlorophenyl)ethoxy]-2',3',5'-tri-o-(tert-butyldimethylsilyl)-adenosine

Product 1

HCID 9910098SonedenosonYield 46.4%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of 2-[2-(4-chlorophenyl)ethoxy]-2′,3′,5′-tri-O-(TERT-butyldimethylsilyl)-adenosine (Example 1, 500 mg, 0.654 mmol) in 7 mL of anhydrous methanol flushed with nitrogen was added 3.27 mL of a 1.0 M solution of TBAF in THF (5 equiv). The reaction was heated to 50° C. for 48 hours. Upon disappearance of the starting material as indicated by LC/MS analysis, the reaction mixture was allowed to cool to room temperature and was concentrated to dryness. Ethyl acetate (20 ml) and water (20 ml) were added and stirred for 5 minutes. The layers were separated and the aqueous layer reextracted with ethyl acetate (2×20 ml). The organic phases were combined, dried over MgSO4 and concentrated to give an oil. The crude material was then purified on silica gel, eluting with a gradient of 0%-10% methanol in CH2Cl2, affording 128 mg (46%) of the desired product as a white solid.

Workup

  1. temperatureto cool to room temperature
  2. concentrationwas concentrated to dryness
  3. additionEthyl acetate (20 ml) and water (20 ml) were added
  4. customThe layers were separated
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated
  7. customto give an oil
  8. customThe crude material was then purified on silica gel
  9. washeluting with a gradient of 0%-10% methanol in CH2Cl2

Sources & evidence

ORD record
ord-fc7e6c8f3b4c485ab4bdc9abd56a676e
Source dataset
uspto-grants-2008_03
Patent number
US07342003B2

Reaction notes

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