Potassium Phosphate, Tribasic → 1-{5-chloro-1-[3-(trifluoromethyl)phenyl]-1H-indol-2-yl}heptan-1-one

HRID 1818617Notes

Reaction equation

HRID 1818617 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6]([C:11](=[O:18])[CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH3:17])=[CH:5]2.I[C:20]1[CH:21]=[C:22]([C:26]([F:29])([F:28])[F:27])[CH:23]=[CH:24][CH:25]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>[Cu](I)I.C1(C)C=CC=CC=1>[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([C:20]1[CH:25]=[CH:24][CH:23]=[C:22]([C:26]([F:29])([F:28])[F:27])[CH:21]=1)[C:6]([C:11](=[O:18])[CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH3:17])=[CH:5]2

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 67868Benzene, 1-iodo-3-(trifluoromethyl)-HCID 66777278HCID 66777278, compound

Product 1

HCID 667789981-{5-chloro-1-[3-(trifluoromethyl)phenyl]-1H-indol-2-yl}heptan-1-one

Reagents, catalysts & solvents 2

HCID 83717Copper iodideCatalystHCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

To a vial containing the title compound of Example 1 Step B (3.0 g, 11.36 mmol), were added 3-iodobenzotrifluoride (1.97 mL, 13.6 mmol), copper iodide (218 mg, 1.14 mmol), potassium phosphate (5.05 g, 23.9 mmol), and 1,2-trans-N,N-dimethylcyclohexane diamine (0.718 mL, 4.54 mmol). The reaction mixture was placed under a nitrogen atmosphere, and anhydrous toluene (11.4 mL, deoxygenated via nitrogen sparge) was added. The vial was then capped and placed in a pre-heated oil bath (110° C.) and stirred rapidly for 19 h. The mixture was allowed to cool to room temperature, then was filtered. The supernatant was washed extensively with EtOAc, and the organic phase was concentrated in vacuo. Purification by flash chromatography (10% EtOAc in hexanes) afforded the title compound: LCMS B, tr=3.02 min, m/z 408.2 [M+H]+; 1H NMR (500 MHz, CDCl3) δ 7.74-7.72 (m, 2H), 7.64 (t, J=8.0 Hz, 1H), 7.52 (s, 1H), 7.46 (d, J=8.0 Hz, 1H), 7.37 (s, 1H), 7.26 (dd, J=9.0, 2.0 Hz, 1H), 6.96 (d, J=9.0 Hz, 1H), 2.94 (t, J=7.5 Hz, 2H), 1.68 (quint., J=7.5 Hz, 2H), 1.38-1.28 (m, 6H), 0.88 (t, J=7.0 Hz, 3H).

Workup

  1. customThe vial was then capped
  2. customplaced in a pre-heated oil bath
  3. temperatureto cool to room temperature
  4. filtrationwas filtered
  5. washThe supernatant was washed extensively with EtOAc
  6. concentrationthe organic phase was concentrated in vacuo
  7. customPurification by flash chromatography (10% EtOAc in hexanes)

Sources & evidence

ORD record
ord-0ea74e0ed2aa4caf9fe0a2ad42eb575d
Source dataset
uspto-grants-2009_10
Patent number
US07598398B2

Reaction notes

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