2-Bromopropene → 2-(2-propenyl)indole
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.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
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), Cul (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
- customthe suspension degassed
- customby bubbling Ar for 20 min
- customafter degassing for an additional 10 min
- additionThe suspension was then diluted with TBME (100 mL)
- washwashed with brine (2×25 mL)
- dry with materialThe extract was dried (MgSO4)
- concentrationconcentrated under reduced pressure
- customto give a residue that
- customwas purified by flash chromatography
Sources & evidence
- ORD record
- ord-1097d2ec966f491b81bb862a66643755
- Source dataset
- uspto-grants-2011_10
- Patent number
- US08030309B2
Reaction notes
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