Water → [(S)-2-phenyl-1-(6-trimethylsilanylethynyl-1H-benzoimidazol-2-yl)-ethyl]-carbamic acid tert-butyl ester

HRID 227162Notes

Reaction equation

HRID 227162 reaction equation
[C:1]([O:5][C:6](=[O:26])[NH:7][C@H:8]([C:16]1[NH:20][C:19]2[CH:21]=[CH:22][C:23](I)=[CH:24][C:18]=2[N:17]=1)[CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.[CH3:34][Si:35]([C:38]#[CH:39])([CH3:37])[CH3:36].O>CN(C)C=O.[Cu]I.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C(OCC)(=O)C>[C:1]([O:5][C:6](=[O:26])[NH:7][C@H:8]([C:16]1[NH:17][C:18]2[CH:24]=[C:23]([C:39]#[C:38][Si:35]([CH3:37])([CH3:36])[CH3:34])[CH:22]=[CH:21][C:19]=2[N:20]=1)[CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

9

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 66111TrimethylsilylacetyleneHCID 178454142HCID 178454142, compound

Product 1

HCID 66815258[(S)-2-phenyl-1-(6-trimethylsilanylethynyl-1H-benzoimidazol-2-yl)-ethyl]-carbamic acid tert-butyl esterYield 96.1%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of [(S)-1-(5-iodo-1H-benzoimidazol-2-yl)-2-phenyl-ethyl]-carbamic acid tert-butyl ester (100 mg, 0.216 mmol), copper (I) iodide (8 mg, 0.043 mmol) and dichlorobis(triphenylphosphine)palladium (II) (15 mg, 0.022 mmol) in N,N-dimethylformamide (7 mL) in a sealed tube apparatus was degassed with dry nitrogen. The yellow mixture was stirred at room temperature for an additional 5 minutes, then triethylamine (90 μL, 0.648 mmol) and trimethylsilylacetylene (92 μL, 0.648 mmol) were added, and the resulting solution was degassed once more After stirring the reaction mixture for 5 minutes at room temperature a deep red to black solution resulted. This mixture was left to stir overnight at room temperature then poured into a separatory funnel containing water (50 mL) and ethyl acetate (50 mL). The aqueous layer was separated and extracted twice with ethyl acetate (20 mL). The combined organic layers were dried over sodium sulfate, filtered and concentrated in vacuo. The residue was applied to a silica gel column using dichloromethane (10 mL) and gradient eluted from 10 to 100% v/v ethyl acetate in hexanes to give [(S)-2-phenyl-1-(6-trimethylsilanylethynyl-1H-benzoimidazol-2-yl)-ethyl]-carbamic acid tert-butyl ester (90 mg, 96%).

Workup

  1. customthe resulting solution was degassed once more
  2. stirringAfter stirring the reaction mixture for 5 minutes at room temperature a deep red to black solution
  3. customresulted
  4. waitThis mixture was left
  5. stirringto stir overnight at room temperature
  6. additionthen poured into a separatory funnel
  7. customThe aqueous layer was separated
  8. extractionextracted twice with ethyl acetate (20 mL)
  9. dry with materialThe combined organic layers were dried over sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. washgradient eluted from 10 to 100% v/v ethyl acetate in hexanes

Sources & evidence

ORD record
ord-4c1c223545cd45f5a7d2889a925fad71
Source dataset
uspto-grants-2009_07
Patent number
US07557221B2

Reaction notes

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