Sulfuric Acid → HCID 59454915, compound

HRID 1401449Notes

Reaction equation

HRID 1401449 reaction equation
[Cl:1][C:2]1[CH:10]=[CH:9][C:8]2[N:7]([CH2:11][C:12]([C:15]3[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[C:17]([F:23])[CH:16]=3)(O)[CH3:13])[C:6]3[CH2:24][CH2:25][N:26]([CH3:28])[CH2:27][C:5]=3[C:4]=2[CH:3]=1.S(=O)(=O)(O)O.[OH-].[K+]>>[Cl:1][C:2]1[CH:10]=[CH:9][C:8]2[N:7](/[CH:11]=[C:12](/[C:15]3[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[C:17]([F:23])[CH:16]=3)\[CH3:13])[C:6]3[CH2:24][CH2:25][N:26]([CH3:28])[CH2:27][C:5]=3[C:4]=2[CH:3]=1.[Cl:1][C:2]1[CH:10]=[CH:9][C:8]2[N:7]([CH2:11][C:12]([C:15]3[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[C:17]([F:23])[CH:16]=3)=[CH2:13])[C:6]3[CH2:24][CH2:25][N:26]([CH3:28])[CH2:27][C:5]=3[C:4]=2[CH:3]=1

Participants

5

Reactant 3

HCID 1118Sulfuric AcidHCID 14797Potassium HydroxideHCID 49779708HCID 49779708, compound

Product 2

HCID 59454915HCID 59454915, compoundHCID 59455072HCID 59455072, compound

Conditions

Temperature
5 °C

Procedure

1-(8-Chloro-1,2,3,4-tetrahydro-2-methylpyrido[4,3-b]indol-5-yl)-2-(3-fluoro-4-methoxyphenyl)propan-2-ol (1 equiv.) was refluxed with 25% sulfuric acid for 2 h. The reaction mixture was cooled to 5° C. with an ice-water bath. KOH (15% aq. solution) was added dropwise to the reaction mixture until pH 9-10 was achieved. The reaction mixture was extracted with EtOAc. The combined organic layers were washed with water followed by brine, dried over sodium sulfate and evaporated under vacuum. The crude product was purified by column chromatography over silica gel (100-200 mesh) using a gradient of MeOH-EtOAc (0-10%) to obtain 8-chloro-5-((E)-2-(3-fluoro-4-methoxyphenyl)prop-1-enyl)-2,3,4,5-tetrahydro-2-methyl-1H-pyrido[4,3-b]indole and 8-chloro-5-(2-(3-fluoro-4-methoxyphenyl)allyl)-2,3,4,5-tetrahydro-2-methyl-1H-pyrido[4,3-b]indole, which were separated by HPLC.

Workup

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

Sources & evidence

ORD record
ord-8a35d03ae8e2476dbb396d2663431289
Source dataset
uspto-grants-2014_12
Patent number
US08907097B2

Reaction notes

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