Sulfuric Acid → 5-(3-fluoro-4-methoxystyryl)-8-chloro-2,3,4,5-tetrahydro-2-methyl-1H-pyrido[4,3-b]indole

HRID 1400377Notes

Reaction equation

HRID 1400377 reaction equation
[Cl:1][C:2]1[CH:10]=[CH:9][C:8]2[N:7]([CH2:11][CH:12]([C:14]3[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[C:16]([F:22])[CH:15]=3)O)[C:6]3[CH2:23][CH2:24][N:25]([CH3:27])[CH2:26][C:5]=3[C:4]=2[CH:3]=1.S(=O)(=O)(O)O.[OH-].[K+]>>[F:22][C:16]1[CH:15]=[C:14]([CH:19]=[CH:18][C:17]=1[O:20][CH3:21])[CH:12]=[CH:11][N:7]1[C:8]2[CH:9]=[CH:10][C:2]([Cl:1])=[CH:3][C:4]=2[C:5]2[CH2:26][N:25]([CH3:27])[CH2:24][CH2:23][C:6]1=2

Participants

4

Reactant 3

HCID 1118Sulfuric AcidHCID 14797Potassium HydroxideHCID 578761572-(8-Chloro-1,2,3,4-tetrahydro-2-methylpyrido[4,3-b]indol-5-yl)-1-(3-fluoro-4-methoxyphenyl)ethanol

Product 1

HCID 684882295-(3-fluoro-4-methoxystyryl)-8-chloro-2,3,4,5-tetrahydro-2-methyl-1H-pyrido[4,3-b]indole

Conditions

Temperature
5 °C

Procedure

2-(8-Chloro-1,2,3,4-tetrahydro-2-methylpyrido[4,3-b]indol-5-yl)-1-(3-fluoro-4-methoxyphenyl)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

  1. extractionThe reaction mixture is extracted with EtOAc
  2. washThe combined organic layers are washed with water
  3. dry with materialdried over sodium sulfate
  4. customevaporated under vacuum
  5. customThe crude product is purified by column chromatography over silica gel (100-200 mesh)

Sources & evidence

ORD record
ord-29f6398ed96e4dbfbf71b3a29bbb2f86
Source dataset
uspto-grants-2014_12
Patent number
US08906925B2

Reaction notes

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