Sulfuric Acid → 5-(2-(4-fluorophenyl)allyl)-2,3,4,5-tetrahydro-2,8-dimethyl-1H-pyrido[4,3-b]indole

HRID 1401447Notes

Reaction equation

HRID 1401447 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](O)([CH3:25])[CH2:9][N:10]2[C:18]3[CH:17]=[CH:16][C:15]([CH3:19])=[CH:14][C:13]=3[C:12]3[CH2:20][N:21]([CH3:24])[CH2:22][CH2:23][C:11]2=3)=[CH:4][CH:3]=1.S(=O)(=O)(O)O.[OH-].[K+].[F:34][C:35]1[CH:40]=[CH:39][C:38](/[C:41](/[CH3:58])=[CH:42]\[N:43]2[C:51]3[CH:50]=[CH:49][C:48]([CH3:52])=[CH:47][C:46]=3[C:45]3[CH2:53][N:54]([CH3:57])[CH2:55][CH2:56][C:44]2=3)=[CH:37][CH:36]=1>CCOC(C)=O>[F:1][C:2]1[CH:3]=[CH:4][C:5](/[C:8](/[CH3:25])=[CH:9]/[N:10]2[C:18]3[CH:17]=[CH:16][C:15]([CH3:19])=[CH:14][C:13]=3[C:12]3[CH2:20][N:21]([CH3:24])[CH2:22][CH2:23][C:11]2=3)=[CH:6][CH:7]=1.[F:34][C:35]1[CH:36]=[CH:37][C:38]([C:41](=[CH2:58])[CH2:42][N:43]2[C:51]3[CH:50]=[CH:49][C:48]([CH3:52])=[CH:47][C:46]=3[C:45]3[CH2:53][N:54]([CH3:57])[CH2:55][CH2:56][C:44]2=3)=[CH:39][CH:40]=1

Participants

7

Reactant 4

HCID 1118Sulfuric AcidHCID 14797Potassium HydroxideHCID 461995815-((Z)-2-(4-fluorophenyl)prop-1-enyl)-2,3,4,5-tetrahydro-2,8-dimethyl-1H-pyrido[4,3-b]indoleHCID 578761042-(4-Fluorophenyl)-1-(1,2,3,4-tetrahydro-2,8-dimethylpyrido[4,3-b]indol-5-yl)propan-2-ol

Product 2

HCID 594548975-(2-(4-fluorophenyl)allyl)-2,3,4,5-tetrahydro-2,8-dimethyl-1H-pyrido[4,3-b]indoleHCID 59455237(E)-5-(2-(4-fluorophenyl)prop-1-enyl)-2,3,4,5-tetrahydro-2,8-dimethyl-1H-pyrido[4,3-b]indole

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
2.5 °C

Procedure

2-(4-Fluorophenyl)-1-(1,2,3,4-tetrahydro-2,8-dimethylpyrido[4,3-b]indol-5-yl)propan-2-ol (4.6 g, 13.05 mmol, 1 equiv.) was heated to reflux with 14 mL of 25% aq. sulfuric acid for 2 h. The reaction mixture was cooled to 0-5° C. and made alkaline with 15% aq. KOH solution and extracted with THF:EtOAc (1:1 mixture, 2×30 mL). The combined organic layer was washed with water (15 mL) and then brine, dried over sodium sulfate and evaporated under vacuum. 4.1 g of crude product was obtained which contained 5-((Z)-2-(4-fluorophenyl)prop-1-enyl)-2,3,4,5-tetrahydro-2,8-dimethyl-1H-pyrido[4,3-b]indole as the minor isomer. This isomer was isolated by repeated flash chromatography using 230-400 mesh silica gel using EtOAc as eluent. Yield: 500 mg of 5-((E)-2-(4-fluorophenyl)prop-1-enyl)-2,3,4,5-tetrahydro-2,8-dimethyl-1H-pyrido[4,3-b]indole and 1 g of 5-(2-(4-fluorophenyl)allyl)-2,3,4,5-tetrahydro-2,8-dimethyl-1H-pyrido[4,3-b]indole were isolated as pure products.

Workup

  1. extractionextracted with THF:EtOAc (1:1 mixture, 2×30 mL)
  2. washThe combined organic layer was washed with water (15 mL)
  3. dry with materialbrine, dried over sodium sulfate
  4. customevaporated under vacuum
  5. custom4.1 g of crude product was obtained which
  6. customThis isomer was isolated by repeated flash chromatography

Sources & evidence

ORD record
ord-2b41244211574672889631a5d427d0f8
Source dataset
uspto-grants-2014_12
Patent number
US08907097B2

Reaction notes

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