Trifluoroacetic acid → HCID 58392454, compound

HRID 561681Notes

Reaction equation

HRID 561681 reaction equation
[Cl-].[In+3].[Cl-].[Cl-].FC(F)(F)C(O)=O.[Cl:12][C:13]1[CH:18]=[CH:17][C:16]([CH:19]([CH:21]2[CH2:23][C:22]2([F:25])[F:24])O)=[CH:15][CH:14]=1.[F:26][C:27]1[CH:28]=[C:29]2[C:33](=[C:34]([CH2:36][S:37]([CH3:40])(=[O:39])=[O:38])[CH:35]=1)[NH:32][CH:31]=[CH:30]2>ClCCCl>[Cl:12][C:13]1[CH:18]=[CH:17][C:16]([CH:19]([CH:21]2[CH2:23][C:22]2([F:25])[F:24])[C:30]2[C:29]3[C:33](=[C:34]([CH2:36][S:37]([CH3:40])(=[O:38])=[O:39])[CH:35]=[C:27]([F:26])[CH:28]=3)[NH:32][CH:31]=2)=[CH:15][CH:14]=1

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 159675indium(III)chlorideHCID 583923185-Fluoro-7-[(methylsulfonyl)methyl]-1H-indoleHCID 58392413(4-Chlorophenyl)(2,2-difluorocyclopropyl)methanol

Product 1

HCID 58392454HCID 58392454, compound

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

97.1 mg (0.44 mmol) of indium(III) chloride and 0.05 ml (0.07 mmol) of trifluoroacetic acid were added to 80.0 mg (0.37 mmol) of the compound from Example 159A and 100 mg (0.44 mmol) of the compound from Example 87A in 4 ml of 1,2-dichloroethane, and the mixture was heated under reflux overnight. It was concentrated and the residue was taken up in ethyl acetate and washed with saturated aqueous sodium bicarbonate solution and saturated aqueous sodium chloride solution, dried over sodium sulfate, filtered and concentrated. The residue was purified by preparative HPLC (RP18 column; mobile phase: acetonitrile/water gradient with addition of 0.1% formic acid) to result in 6.0 mg (4% of theory) of the title compound as mixture of diastereomers.

Workup

  1. temperaturethe mixture was heated
  2. temperatureunder reflux overnight
  3. concentrationIt was concentrated
  4. washwashed with saturated aqueous sodium bicarbonate solution and saturated aqueous sodium chloride solution
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by preparative HPLC (RP18 column; mobile phase: acetonitrile/water gradient with addition of 0.1% formic acid)

Sources & evidence

ORD record
ord-ff602075e8c14e479ad01e3a9d396931
Source dataset
uspto-grants-2011_11
Patent number
US08063234B2

Reaction notes

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