Ammonium fluoride → 2-(2-Cyclohexylethoxy)-9-pentofuranosyl-9H-purin-6-amine

HRID 1392009Notes

Reaction equation

HRID 1392009 reaction equation
[CH:1]1([CH2:7][CH2:8][O:9][C:10]2[N:11]=[C:12]([NH2:49])[C:13]3[N:14]=[CH:15][N:16]([C:47]=3[N:48]=2)[C@@H:17]2[O:46][C@H:36]([CH2:37][O:38][Si](C(C)(C)C)(C)C)[C@@H:27]([O:28][Si](C(C)(C)C)(C)C)[C@H:18]2[O:19][Si](C(C)(C)C)(C)C)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[F-].[NH4+]>CO>[CH:1]1([CH2:7][CH2:8][O:9][C:10]2[N:11]=[C:12]([NH2:49])[C:13]3[N:14]=[CH:15][N:16]([C:47]=3[N:48]=2)[C@@H:17]2[O:46][C@H:36]([CH2:37][OH:38])[C@@H:27]([OH:28])[C@H:18]2[OH:19])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

4

Reactant 2

HCID 25516Ammonium fluorideHCID 58661652HCID 58661652, compound

Product 1

HCID 1314502-(2-Cyclohexylethoxy)-9-pentofuranosyl-9H-purin-6-amine

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a 100-mL one-neck round bottom flask was added under a nitrogen atmosphere 2-[2-(cyclohexyl)ethoxy]-2′,3′,5′-tri-O-(TERT-butyldimethylsilyl)-adenosine (3.3 g, Example 10), anhydrous methanol (50 mL), and ammonium fluoride (1.7 g, 45.8 mmol). The resulting solution was heated to reflux for 24 hours, at which time HPLC indicated the disappearance of starting material. The reaction was cooled to room temperature, concentrated in vacuo on a rotary evaporator, and the resultant solids partitioned between ethyl acetate (50 mL) and water (30 mL). The mixture was stirred for 10 minutes, the layers separated, and the aqueous portion extracted with additional ethyl acetate (50 mL). The combined organic layers were dried (MgSO4), filtered, and concentrated to a light yellow solid. The product was purified by passing the oil through a plug of silica gel, eluting with CH2Cl2, 2% methanol in CH2Cl2, 5% methanol in CH2Cl2, and 10% methanol in CH2Cl2. Fractions containing the product were combined and concentrated at reduced pressure to afford the desired product as a white solid. 1.2 g (39%). m.p.: 105–112° C.

Workup

  1. temperatureThe resulting solution was heated
  2. temperatureto reflux for 24 hours, at which time HPLC
  3. concentrationconcentrated in vacuo on a rotary evaporator
  4. customthe resultant solids partitioned between ethyl acetate (50 mL) and water (30 mL)
  5. customthe layers separated
  6. extractionthe aqueous portion extracted with additional ethyl acetate (50 mL)
  7. dry with materialThe combined organic layers were dried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated to a light yellow solid
  10. customThe product was purified
  11. washeluting with CH2Cl2, 2% methanol in CH2Cl2, 5% methanol in CH2Cl2
  12. additionFractions containing the product
  13. concentrationconcentrated at reduced pressure

Sources & evidence

ORD record
ord-9b5fbcc619b0473ebe620cc39a018284
Source dataset
uspto-grants-2008_03
Patent number
US07342003B2

Reaction notes

Loading…