Trifluoroacetic acid → 3-[(4-Chlorophenyl)(2,2-difluorocyclopropyl)methyl]-7-[(methylsulfonyl)methyl]-1H-indole

HRID 561680Notes

Reaction equation

HRID 561680 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.[CH3:26][S:27]([CH2:30][C:31]1[CH:32]=[CH:33][CH:34]=[C:35]2[C:39]=1[NH:38][CH:37]=[CH:36]2)(=[O:29])=[O:28]>ClCCCl.ClCCl>[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:36]2[C:35]3[C:39](=[C:31]([CH2:30][S:27]([CH3:26])(=[O:29])=[O:28])[CH:32]=[CH:33][CH:34]=3)[NH:38][CH:37]=2)=[CH:15][CH:14]=1

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 159675indium(III)chlorideHCID 583922947-[(Methylsulfonyl)methyl]-1H-indoleHCID 58392413(4-Chlorophenyl)(2,2-difluorocyclopropyl)methanol

Product 1

HCID 583921923-[(4-Chlorophenyl)(2,2-difluorocyclopropyl)methyl]-7-[(methylsulfonyl)methyl]-1H-indole

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 6344DichloromethaneSolvent

Procedure

In three parallel batches in each case 3.08 g (13.9 mmol) of indium(III) chloride and 1.6 ml (20.9 mmol) of trifluoroacetic acid were added to in each case 2.54 g (11.6 mmol) of the compound from Example 159A and 2.92 g (13.9 mmol) of the compound from Example 86A in 125 ml of 1,2-dichloroethane, and the mixture was heated under reflux overnight. It was diluted in each case with dichloromethane, and the three batches were combined and washed with saturated aqueous sodium bicarbonate solution, water and saturated aqueous sodium chloride solution, dried over magnesium sulfate, filtered through kieselguhr and concentrated. The residue was purified by preparative SFC (ethylpyridine column; mobile phase: carbon dioxide/methanol gradient; 150 bar; 35° C.) to result in 995 mg (7% of theory) of the title compound as mixture of diastereomers.

Workup

  1. temperaturethe mixture was heated
  2. temperatureunder reflux overnight
  3. washwashed with saturated aqueous sodium bicarbonate solution, water and saturated aqueous sodium chloride solution
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered through kieselguhr
  6. concentrationconcentrated
  7. customThe residue was purified by preparative SFC (ethylpyridine column; mobile phase: carbon dioxide/methanol gradient; 150 bar; 35° C.)

Sources & evidence

ORD record
ord-e2512a05c353428685d6fef2d48f6ad7
Source dataset
uspto-grants-2011_11
Patent number
US08063234B2

Reaction notes

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