Sulfuric Acid → 5-((E)-2-(5-(trifluoromethyl)pyridin-3-yl)vinyl)-2,3,4,5-tetrahydro-2,8-dimethyl-1H-pyrido[4,3-b]indole
Reaction equation
[F:1][C:2]([F:28])([F:27])[C:3]1[CH:4]=[C:5]([CH:9](O)[CH2:10][N:11]2[C:19]3[CH:18]=[CH:17][C:16]([CH3:20])=[CH:15][C:14]=3[C:13]3[CH2:21][N:22]([CH3:25])[CH2:23][CH2:24][C:12]2=3)[CH:6]=[N:7][CH:8]=1.S(=O)(=O)(O)O.[OH-].[K+]>>[F:27][C:2]([F:1])([F:28])[C:3]1[CH:4]=[C:5](/[CH:9]=[CH:10]/[N:11]2[C:19]3[CH:18]=[CH:17][C:16]([CH3:20])=[CH:15][C:14]=3[C:13]3[CH2:21][N:22]([CH3:25])[CH2:23][CH2:24][C:12]2=3)[CH:6]=[N:7][CH:8]=1Participants
4
Reactant 3
Product 1
Conditions
- Temperature
- 5 °C
Procedure
1-(5-(Trifluoromethyl)pyridin-3-yl)-2-(1,2,3,4-tetrahydro-2,8-dimethylpyrido[4,3-b]indol-5-yl)ethanol (1 equiv.) is refluxed with 25% sulfuric acid for 2 h. The reaction mixture is cooled to 5° C. with an ice-water bath. KOH (15% aq. solution) is added dropwise to the reaction mixture until pH 9-10 is achieved. The reaction mixture is extracted with EtOAc. The combined organic layers are washed with water followed by brine, dried over sodium sulfate and evaporated under vacuum. The crude product is purified by column chromatography over silica gel (100-200 mesh) using a gradient of MeOH-EtOAc (0-10%).
Workup
- extractionThe reaction mixture is extracted with EtOAc
- washThe combined organic layers are washed with water
- dry with materialdried over sodium sulfate
- customevaporated under vacuum
- customThe crude product is purified by column chromatography over silica gel (100-200 mesh)
Sources & evidence
- ORD record
- ord-c14050ee446944a38d5a1ca28948dc94
- Source dataset
- uspto-grants-2014_12
- Patent number
- US08906925B2
Reaction notes
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