Cyclopropylacetylene → 2-cyclopropyl-1H-indole

HRID 491028Notes

Reaction equation

HRID 491028 reaction equation
I[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[NH:8][C:9](=O)[CH3:10].[CH:12]1(C#C)[CH2:14][CH2:13]1>O1CCOCC1.CN(C)C(N(C)C)=N.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.[Cu]I>[CH:12]1([C:9]2[NH:8][C:3]3[C:4]([CH:10]=2)=[CH:5][CH:6]=[CH:7][CH:2]=3)[CH2:14][CH2:13]1

Participants

7

Reactant 2

HCID 138823CyclopropylacetyleneHCID 1405592'-Iodoacetanilide

Product 1

HCID 113895272-cyclopropyl-1H-indole

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 312751,4-DioxaneSolvent2×HCID 664601,1,3,3-TetramethylguanidineSolvent2×

Conditions

Temperature
80 °C

Procedure

To a solution of N-(2-iodophenyl)acetamide (100 mg, 0.38 mmol) in dioxane (750 mL) and 1,1,3,3-tetramethylguanidine (750 mL) was added cyclopropylacetylene (41 mL, 0.49 mmol), bis(triphenylphosphine)palladium(II) chloride (35 mg, 0.05 mmol), and copper(I) iodide (10 mg, 0.05 mmol). The reaction was stirred overnight at 80° C. The solution was cooled and partitioned between water and methylene chloride. The organic layer was dried (MgSO4) and concentrated to give the uncyclized Sonagashira coupling product. Dioxane (750 mL) and 1,1,3,3-tetramethylguanidine (750 mL) were added and the reaction was stirred overnight at 90° C. The solution was again partitioned between water and methylene chloride. The organic layer was dried (MgSO4) and concentrated to give the desired indole, which was used without further purification.

Workup

  1. temperatureThe solution was cooled
  2. custompartitioned between water and methylene chloride
  3. dry with materialThe organic layer was dried (MgSO4)
  4. concentrationconcentrated
  5. customto give the uncyclized Sonagashira coupling product
  6. stirringthe reaction was stirred overnight at 90° C
  7. customThe solution was again partitioned between water and methylene chloride
  8. dry with materialThe organic layer was dried (MgSO4)
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-da5ab6b258164f2dbe0297179072e959
Source dataset
uspto-grants-2009_05
Patent number
US07528262B2

Reaction notes

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