Trifluoroacetic acid → 2-({5-Fluoro-7-[(methylsulfonyl)methyl]-1H-indol-3-yl}[4-(trifluoromethyl)phenyl]methyl)cyclopropanecarbonitrile

HRID 561691Notes

Reaction equation

HRID 561691 reaction equation
[Cl-].[In+3].[Cl-].[Cl-].FC(F)(F)C(O)=O.O[CH:13]([C:19]1[CH:24]=[CH:23][C:22]([C:25]([F:28])([F:27])[F:26])=[CH:21][CH:20]=1)[CH:14]1[CH2:16][CH:15]1[C:17]#[N:18].[F:29][C:30]1[CH:31]=[C:32]2[C:36](=[C:37]([CH2:39][S:40]([CH3:43])(=[O:42])=[O:41])[CH:38]=1)[NH:35][CH:34]=[CH:33]2>ClCCCl>[F:29][C:30]1[CH:31]=[C:32]2[C:36](=[C:37]([CH2:39][S:40]([CH3:43])(=[O:41])=[O:42])[CH:38]=1)[NH:35][CH:34]=[C:33]2[CH:13]([C:19]1[CH:24]=[CH:23][C:22]([C:25]([F:28])([F:27])[F:26])=[CH:21][CH:20]=1)[CH:14]1[CH2:16][CH:15]1[C:17]#[N:18]

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 159675indium(III)chlorideHCID 583923185-Fluoro-7-[(methylsulfonyl)methyl]-1H-indoleHCID 583924082-{Hydroxy[4-(trifluoromethyl)phenyl]methyl}cyclopropanecarbonitrile

Product 1

HCID 583925102-({5-Fluoro-7-[(methylsulfonyl)methyl]-1H-indol-3-yl}[4-(trifluoromethyl)phenyl]methyl)cyclopropanecarbonitrile

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

33.0 mg (0.15 mmol) of indium(III) chloride and 0.02 ml (0.22 mmol) of trifluoroacetic acid were added to 30.0 mg (0.12 mmol) of the compound from Example 160A and 41.4 mg (0.15 mmol) of the compound from Example 87A with a purity of 82% under argon in 1 ml of 1,2-dichloroethane, and the mixture was heated under reflux for three days. It was concentrated and the residue was taken up in ethyl acetate, 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 12.6 mg (23% of theory) of diastereomer 1 and 13.2 mg (24% of theory) of diastereomer 2 of the title compound.

Workup

  1. temperaturethe mixture was heated
  2. temperatureunder reflux for three days
  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-3a4376cbeb9242fb9bb63f64fdb5ea52
Source dataset
uspto-grants-2011_11
Patent number
US08063234B2

Reaction notes

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