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

HRID 561682Notes

Reaction equation

HRID 561682 reaction equation
[Cl-].[In+3].[Cl-].[Cl-].FC(F)(F)C(O)=O.[F:12][C:13]1[CH:14]=[C:15]2[C:19](=[C:20]([CH2:22][S:23]([CH3:26])(=[O:25])=[O:24])[CH:21]=1)[NH:18][CH:17]=[CH:16]2.O[CH:28]([C:34]1[CH:39]=[CH:38][C:37]([CH3:40])=[CH:36][CH:35]=1)[CH:29]1[CH2:31][CH:30]1[C:32]#[N:33]>ClCCCl.ClCCl>[F:12][C:13]1[CH:14]=[C:15]2[C:19](=[C:20]([CH2:22][S:23]([CH3:26])(=[O:24])=[O:25])[CH:21]=1)[NH:18][CH:17]=[C:16]2[CH:28]([C:34]1[CH:35]=[CH:36][C:37]([CH3:40])=[CH:38][CH:39]=1)[CH:29]1[CH2:31][CH:30]1[C:32]#[N:33]

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 159675indium(III)chlorideHCID 583923185-Fluoro-7-[(methylsulfonyl)methyl]-1H-indoleHCID 583923442-[Hydroxy(4-methylphenyl)methyl]cyclopropanecarbonitrile

Product 1

HCID 583925252-[{5-Fluoro-7-[(methylsulfonyl)methyl]-1H-indol-3-yl}(4-methylphenyl)methyl]cyclopropane-carbonitrile

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 6344DichloromethaneSolvent

Procedure

3.63 g (16.4 mmol) of indium(III) chloride and 1.9 ml (24.6 mmol) of trifluoroacetic acid were added to 4.23 g (16.4 mmol) of the compound from Example 87A and 2.56 g (13.7 mmol) of the compound from Example 158A under argon in 300 ml of 1,2-dichloroethane, and the mixture was stirred under reflux for 4 h. It was diluted with dichloromethane and washed with water and saturated aqueous sodium bicarbonate solution, dried over magnesium 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 3.16 g (49% of theory) of the title compound as mixture of diastereomers.

Workup

  1. temperatureunder reflux for 4 h
  2. washwashed with water and saturated aqueous sodium bicarbonate solution
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. 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-18e1deab0be44731af3ce5d2d63a79a6
Source dataset
uspto-grants-2011_11
Patent number
US08063234B2

Reaction notes

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