2-Cyclohexylethanol → HCID 58661652, compound

HRID 1392008Notes

Reaction equation

HRID 1392008 reaction equation
Cl[C:2]1[N:3]=[C:4]([NH2:41])[C:5]2[N:6]=[CH:7][N:8]([C:39]=2[N:40]=1)[C@@H:9]1[O:38][C@H:28]([CH2:29][O:30][Si:31]([C:34]([CH3:37])([CH3:36])[CH3:35])([CH3:33])[CH3:32])[C@@H:19]([O:20][Si:21]([C:24]([CH3:27])([CH3:26])[CH3:25])([CH3:23])[CH3:22])[C@H:10]1[O:11][Si:12]([C:15]([CH3:18])([CH3:17])[CH3:16])([CH3:14])[CH3:13].[CH:42]1([CH2:48][CH2:49][OH:50])[CH2:47][CH2:46][CH2:45][CH2:44][CH2:43]1>>[CH:42]1([CH2:48][CH2:49][O:50][C:2]2[N:3]=[C:4]([NH2:41])[C:5]3[N:6]=[CH:7][N:8]([C:39]=3[N:40]=2)[C@@H:9]2[O:38][C@H:28]([CH2:29][O:30][Si:31]([C:34]([CH3:37])([CH3:36])[CH3:35])([CH3:33])[CH3:32])[C@@H:19]([O:20][Si:21]([C:24]([CH3:27])([CH3:26])[CH3:25])([CH3:23])[CH3:22])[C@H:10]2[O:11][Si:12]([C:15]([CH3:18])([CH3:17])[CH3:16])([CH3:14])[CH3:13])[CH2:47][CH2:46][CH2:45][CH2:44][CH2:43]1

Participants

3

Reactant 2

HCID 205082-CyclohexylethanolHCID 107467489-[(2R,3R,4R,5R)-3,4-bis[[tert-butyl(dimethyl)silyl]oxy]-5-[[tert-butyl(dimethyl)silyl]oxymethyl]oxolan-2-yl]-2-chloropurin-6-amine

Product 1

HCID 58661652HCID 58661652, compound

Conditions

Temperature
50 °C

Procedure

To a dry 250-mL, 3-neck roundbottom flask was added 2-chloro-2′,3′,5′-tri-O-(TERT-butyldimethylsilyl)adenosine (5 g, 7.8 mmol, Example 1) and 2-(cyclohexyl)ethanol (15 mL). The mixture was flushed with nitrogen for 5–10 minutes, then heated to 50° C. To this mixture was added sodium hydride (1.56 g, 39 mmol, as a 60% dispersion in mineral oil) at such a rate as to avoid excessive gas evolution. The reaction was maintained at 50° C. until the reaction was complete by HPLC. The reaction was then cooled to room temperature, carefully quenched with water (50 mL), and extracted with ethyl acetate (100 mL, 2×60 mL). The combined organic extracts were washed with brine (100 mL), dried (MgSO4), filtered, and concentrated under reduced pressure to afford a viscous oil. This material was purified by passing through a plug of silica gel, eluting with CH2Cl2, 2% MeOH in CH2Cl2, 5% MeOH in CH2Cl2, and 10% MeOH in CH2Cl2. Those fractions containing products were combined and evaporated to dryness, to afford a mixture of monosilyl-protected and disilyl-protected alkylated products (LC/MS m/z=622 and 508). This mixture was used without further purification in the next step.

Workup

  1. customThe mixture was flushed with nitrogen for 5–10 minutes
  2. additionTo this mixture was added sodium hydride (1.56 g, 39 mmol
  3. temperatureThe reaction was maintained at 50° C. until the reaction
  4. temperatureThe reaction was then cooled to room temperature
  5. customcarefully quenched with water (50 mL)
  6. extractionextracted with ethyl acetate (100 mL, 2×60 mL)
  7. washThe combined organic extracts were washed with brine (100 mL)
  8. dry with materialdried (MgSO4)
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customto afford a viscous oil
  12. customThis material was purified
  13. washeluting with CH2Cl2, 2% MeOH in CH2Cl2, 5% MeOH in CH2Cl2
  14. additionThose fractions containing products
  15. customevaporated to dryness
  16. customto afford
  17. additiona mixture of monosilyl-protected and disilyl-protected alkylated products (LC/MS m/z=622 and 508)
  18. customThis mixture was used without further purification in the next step

Sources & evidence

ORD record
ord-63221a91f49c47729afa2206dd81d800
Source dataset
uspto-grants-2008_03
Patent number
US07342003B2

Reaction notes

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