Phenol → HCID 49806225, compound

HRID 1627936Notes

Reaction equation

HRID 1627936 reaction equation
[C:1]1([OH:7])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[H-].[Na+].I[C:11]1[C:16]([CH:17]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])[C:18]([O:20][CH3:21])=[O:19])=[CH:15][N:14]=[C:13]2[S:27][C:28]3[CH2:33][CH2:32][CH2:31][CH2:30][C:29]=3[C:12]=12.O1CCC[CH2:35]1>>[CH3:35][C:15]1[N:14]=[C:13]2[S:27][C:28]3[CH2:33][CH2:32][CH2:31][CH2:30][C:29]=3[C:12]2=[C:11]([O:7][C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[C:16]=1[CH:17]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])[C:18]([O:20][CH3:21])=[O:19]

Participants

5

Reactant 4

HCID 996PhenolHCID 8028Tetrahydrofuran2×HCID 24758Sodium hydrideHCID 66603528HCID 66603528, compound

Product 1

HCID 49806225HCID 49806225, compoundYield 39%

Conditions

Temperature
100 °C

Procedure

Phenol (11.93 mg, 0.127 mmol) was placed in a 2 ml biotage tube, dissolved in tetrahydrofuran (300 μl) and sodium hydride (60%, 5.07 mg, 0.127 mmol) was added. The tube was purged with nitrogen and sealed. After 10 min. a solution of Methyl 2-[4-iodo-5,6,7,8-tetrahydro[1]benzothieno[2,3-b]pyridin-3-yl]-2-tert-butoxyacetate (50 mg, 0.106 mmol) in tetrahydrofuran (300 μl) was added dropwise and the mixture was heated in a sand bath at 100° C. overnight. After cooling, the mixture was partitioned between water and dichloromethane, filtered over a phase separator filter (1PS) and concentrated under reduced pressure. The crude material was purified by flash chromatography on silica gel using a gradient of ethyl acetate (5-40%) in heptane to provide 18 mg (39%) of the title compound as an oil.

Workup

  1. customThe tube was purged with nitrogen
  2. customsealed
  3. temperatureAfter cooling
  4. customthe mixture was partitioned between water and dichloromethane
  5. filtrationfiltered over a phase separator
  6. filtrationfilter (1PS)
  7. concentrationconcentrated under reduced pressure
  8. customThe crude material was purified by flash chromatography on silica gel using a gradient of ethyl acetate (5-40%) in heptane

Sources & evidence

ORD record
ord-9eab52b5616748c49ed9caf41084577d
Source dataset
uspto-grants-2014_07
Patent number
US08785638B2

Reaction notes

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