2-Bromopropene → 2-(2-propenyl)indole

HRID 731125Notes

Reaction equation

HRID 731125 reaction equation
[SnH3][C:2]1[NH:3][C:4]2[C:9]([CH:10]=1)=[CH:8][CH:7]=[CH:6][CH:5]=2.[C:11]1(P(C2C=CC=CC=2)C2C=CC=CC=2)[CH:16]=CC=C[CH:12]=1.[Li+].[Cl-].BrC(C)=C>CN(C=O)C.[Cu]I.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH2:16]([C:2]1[NH:3][C:4]2[C:9]([CH:10]=1)=[CH:8][CH:7]=[CH:6][CH:5]=2)[CH:11]=[CH2:12]

Participants

8

Reactant 4

HCID 112022-BromopropeneHCID 11776TriphenylphosphineHCID 433294Lithium ChlorideHCID 129655202HCID 129655202, compound

Product 1

HCID 100121502-(2-propenyl)indole

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

The 2-stannylindole 23-1 (1.280 g, 2.34 mmol; prepared using methods described in WO 03/010141), triphenylphosphine (0.065 g, 0.25 mmol), CuI (0.045 g, 0.24 mmol), LiCl (0.200 g, 4.72 mmol) and 2-bromopropene (0.444 mL, 5.00 mmol) were dissolved in DMF (6 mL) and the suspension degassed by bubbling Ar for 20 min. Pd2(dba)3 (0.035 g, 0.034 mmol) was added and after degassing for an additional 10 min, the reaction mixture was heated to 100° C. overnight. The suspension was then diluted with TBME (100 mL) and washed with brine (2×25 mL). The extract was dried (MgSO4) and concentrated under reduced pressure to give a residue that was purified by flash chromatography using 5-10% EtOAc in hexane as eluent. The desired 2-(2-propenyl)indole 23-2 was obtained as beige solid (0.57 g, 81% yield): MS-ES m/z 298.1 (MH+). The methyl ester 23-2 was saponified in the usual way (NaOH/DMSO) to give the corresponding carboxylic acid 23-3 in 96% yield: MS-ES m/z 284.1 (MH+).

Workup

  1. customthe suspension degassed
  2. customby bubbling Ar for 20 min
  3. customafter degassing for an additional 10 min
  4. additionThe suspension was then diluted with TBME (100 mL)
  5. washwashed with brine (2×25 mL)
  6. dry with materialThe extract was dried (MgSO4)
  7. concentrationconcentrated under reduced pressure
  8. customto give a residue that
  9. customwas purified by flash chromatography

Sources & evidence

ORD record
ord-58c2ba25824c4a22aa3a6c5378bf095b
Source dataset
uspto-grants-2009_09
Patent number
US07582770B2

Reaction notes

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