Trifluoroacetic acid → 2-[(4-Chlorophenyl){5-fluoro-7-[(methylsulfonyl)methyl]-1H-indol-3-yl}methyl]cyclopropane-carbonitrile

HRID 561696Notes

Reaction equation

HRID 561696 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](O)[CH:20]2[CH2:22][CH:21]2[C:23]#[N:24])=[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]([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:20]2[CH2:22][CH:21]2[C:23]#[N:24])=[CH:15][CH:14]=1

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 159675indium(III)chlorideHCID 583923172-[(4-Chlorophenyl)(hydroxy)methyl]cyclopropanecarbonitrileHCID 583923185-Fluoro-7-[(methylsulfonyl)methyl]-1H-indole

Product 1

HCID 583922532-[(4-Chlorophenyl){5-fluoro-7-[(methylsulfonyl)methyl]-1H-indol-3-yl}methyl]cyclopropane-carbonitrile

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

128 mg (0.58 mmol) of indium(III) chloride and 0.07 ml (0.87 mmol) of trifluoroacetic acid were added to 100 mg (0.48 mmol) of the compound from Example 167A and 149 mg (0.58 mmol) of the compound from Example 87A with a purity of 88% under argon in 5 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, 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 130 mg (65% 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-c2722f0f8941450c900bd751005a7130
Source dataset
uspto-grants-2011_11
Patent number
US08063234B2

Reaction notes

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