Iodobenzene → 4-(2-Ethyl-6-fluoro-1-phenyl-1H-indol-3-YL)-piperidine-1-carboxylic acid tert-butyl ester

HRID 2356388Notes

Reaction equation

HRID 2356388 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[C:22]3[C:17](=[CH:18][C:19]([F:23])=[CH:20][CH:21]=3)[NH:16][C:15]=2[CH2:24][CH3:25])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].P([O-])([O-])([O-])=O.[K+].[K+].[K+].I[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1.CNC1CCCCC1NC>C1(C)C=CC=CC=1.[Cu](I)I.C(OCC)(=O)C.O>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][CH:11]([C:14]2[C:22]3[C:17](=[CH:18][C:19]([F:23])=[CH:20][CH:21]=3)[N:16]([C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=3)[C:15]=2[CH2:24][CH3:25])[CH2:12][CH2:13]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

9

Reactant 4

HCID 11575IodobenzeneHCID 62657Potassium Phosphate, TribasicHCID 5510741-N,2-N-dimethylcyclohexane-1,2-diamineHCID 587479984-(2-ethyl-6-fluoro-1H-indol-3-yl)piperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 587479994-(2-Ethyl-6-fluoro-1-phenyl-1H-indol-3-YL)-piperidine-1-carboxylic acid tert-butyl esterYield 27.3%

Reagents, catalysts & solvents 4

HCID 83717Copper iodideCatalystHCID 962WaterSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 4-(2-ethyl-6-fluoro-1H-indol-3-yl)piperidine-1-carboxylic acid tert-butyl ester (0.36 g) in degassed toluene (10 ml) at r.t., is added potassium phosphate (0.1 g), copper iodide (20 mg), iodobenzene (254 mg) and N,N′-dimethylcyclohexane-1,2-diamine (30 mg). The mixture is heated at reflux for 3 days. Thereafter the mixture is allowed to cool to r.t., and water (20 ml) added. Ethyl acetate (3×10 ml) is used to extract the organic components and the organic layer is washed with water, dried over MgSO4 and concentrated in vacuo. Flash chromatography (9:1 cyclohexane:ethyl acetate) gives 120 mg pure product (27%) as a brown solid.

Workup

  1. temperatureThe mixture is heated
  2. temperatureat reflux for 3 days
  3. extractionto extract the organic components
  4. washthe organic layer is washed with water
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-6a823c4a5e834d72990614dc4283cd01
Source dataset
uspto-grants-2010_07
Patent number
US07759365B2

Reaction notes

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