Sodium hydride → HCID 58661639, compound

HRID 1392013Notes

Reaction equation

HRID 1392013 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].[S:42]1[CH:46]=[CH:45][CH:44]=[C:43]1[CH2:47][CH2:48][OH:49].[H-].[Na+]>>[S:42]1[CH:46]=[CH:45][CH:44]=[C:43]1[CH2:47][CH2:48][O:49][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]

Participants

4

Reactant 3

HCID 24758Sodium hydrideHCID 794002-ThiopheneethanolHCID 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 58661639HCID 58661639, compound

Conditions

Temperature
50 °C

Procedure

A mixture of 2-chloro-2′,3′,5′-tri-O-(tert-butyldimethylsilyl)adenosine) (Example 1, 1.0 g, 1.5 mmol) and 2-(thiophen-2-yl)ethyl alcohol (5 mL) was heated to 50° C. in a roundbottom flask under a nitrogen atmosphere. Sodium hydride (300 mg, 60% dispersion in mineral oil, 7.7 mmol) was added at a rate so as to control gas evolution. Once complete, the reaction was allowed to cool to room temperature and was carefully quenched with 10 mL of water, then extracted with ethyl acetate (3×20 ml). The combined organic phases were washed with 50 mL of brine, dried over MgSO4, and concentrated to give a brown oil that was purified by chromatography on silica gel eluting with a gradient of 0–10% methanol in CH2Cl2. This afforded 361 mg (33%) of 2-[2-(thiophen-2-yl)ethoxy]-2′,3′,5′-tri-O-(TERT-butyldimethylsilyl)adenosine as an off-white solid which was used without further purification

Workup

  1. temperatureto cool to room temperature
  2. customwas carefully quenched with 10 mL of water
  3. extractionextracted with ethyl acetate (3×20 ml)
  4. washThe combined organic phases were washed with 50 mL of brine
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated
  7. customto give a brown oil that
  8. customwas purified by chromatography on silica gel eluting with a gradient of 0–10% methanol in CH2Cl2
  9. customThis afforded 361 mg (33%) of 2-[2-(thiophen-2-yl)ethoxy]-2′,3′,5′-tri-O-(TERT-butyldimethylsilyl)adenosine as an off-white solid which was used without further purification

Sources & evidence

ORD record
ord-73f88f3c221841ba9610e995cacc57ba
Source dataset
uspto-grants-2008_03
Patent number
US07342003B2

Reaction notes

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