Water → 3-{(4-Fluorophenyl)[4-(trifluoromethyl)phenyl]methyl}-7-[(methylsulfanyl)methyl]-1H-indole

HRID 561582

Reaction equation

HRID 561582 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:10]2[CH:15]=[CH:14][C:13]([C:16]([F:19])([F:18])[F:17])=[CH:12][CH:11]=2)O)=[CH:4][CH:3]=1.[Cl-].[In+3].[Cl-].[Cl-].ClC1C=C(Cl)C=CC=1C([C:36]1[C:44]2[C:39](=[C:40]([CH2:46][S:47][CH3:48])[CH:41]=[C:42](F)[CH:43]=2)[NH:38][CH:37]=1)CCO.O>C1(C)C=CC=CC=1.C(OCC)(=O)C>[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:10]2[CH:15]=[CH:14][C:13]([C:16]([F:19])([F:18])[F:17])=[CH:12][CH:11]=2)[C:36]2[C:44]3[C:39](=[C:40]([CH2:46][S:47][CH3:48])[CH:41]=[CH:42][CH:43]=3)[NH:38][CH:37]=2)=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 962WaterHCID 159675indium(III)chloride2×HCID 579773alpha-(4-Fluorophenyl)-4-(trifluoromethyl)benzenemethanolHCID 583923053-(2,4-Dichlorophenyl)-3-{5-fluoro-7-[(methylsulfanyl)methyl]-1H-indol-3-yl}propan-1-ol

Product 1

HCID 583923633-{(4-Fluorophenyl)[4-(trifluoromethyl)phenyl]methyl}-7-[(methylsulfanyl)methyl]-1H-indole

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

503 mg (1.86 mmol) of the compound from Example 80A and 75 mg (0.34 mmol) of indium(III) chloride were added to 300 mg (1.69 mmol) of the compound from Example 8 in 15 ml of toluene. The reaction mixture was stirred at 80° C. for 5 h, a further 187 mg (0.85 mmol) of indium(III) chloride were added, and the mixture was again stirred for 5 h. After cooling to RT, the reaction solution was mixed with water and ethyl acetate, and the solid was filtered off. The phases of the filtrate were separated, and the aqueous phase was extracted with ethyl acetate. The combined organic phases were dried over sodium sulfate, filtered and concentrated. Purification of the crude product by preparative HPLC (mobile phase: acetonitrile/water gradient) resulted in 107 mg (15% of theory) of the title compound.

Workup

  1. stirringthe mixture was again stirred for 5 h
  2. temperatureAfter cooling to RT
  3. filtrationthe solid was filtered off
  4. customThe phases of the filtrate were separated
  5. extractionthe aqueous phase was extracted with ethyl acetate
  6. dry with materialThe combined organic phases were dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customPurification of the crude product by preparative HPLC (mobile phase: acetonitrile/water gradient)

Sources & evidence

ORD record
ord-728b952883bb4306aead89e8d51c5b61
Source dataset
uspto-grants-2011_11
Patent number
US08063234B2

Linked notes

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