Water → (-)-4,5-difluoro-2-(S)-methyl-2,3-dihydroindole p-toluenesulfonate

HRID 2081565Notes

Reaction equation

HRID 2081565 reaction equation
[F:1][C:2]1[C:10]([F:11])=[CH:9][CH:8]=[C:7]2[C:3]=1[CH2:4][C@H:5]([CH3:29])[N:6]2C(=O)[C@@H]1CCCN1[S:18]([C:21]1[CH:26]=[CH:25][C:24]([CH3:27])=[CH:23][CH:22]=1)(=[O:20])=[O:19].[OH-:30].[K+].O>CO>[C:24]1([CH3:27])[CH:23]=[CH:22][C:21]([S:18]([OH:19])(=[O:20])=[O:30])=[CH:26][CH:25]=1.[F:1][C:2]1[C:10]([F:11])=[CH:9][CH:8]=[C:7]2[C:3]=1[CH2:4][C@H:5]([CH3:29])[NH:6]2

Participants

5

Reactant 3

HCID 962WaterHCID 14797Potassium HydroxideHCID 54347967(-)-4,5-difluoro-2-(S)-methyl-1-[(S)-N-p-toluenesulfonylprolyl]-2,3-dihydroindole2×

Product 1

HCID 18649754(-)-4,5-difluoro-2-(S)-methyl-2,3-dihydroindole p-toluenesulfonate

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

(-)-4,5-difluoro-2-(S)-methyl-1-[(S)-N-p-toluenesulfonylprolyl]-2,3-dihydroindole, the compound (a) obtained in Example 1, 51.7 g, was added to the solution comprising 69 g of potassium hydroxide, 50 ml of water and 200 ml of methanol, and the mixture was refluxed by heating for 3.5 hours. After the reaction the mixture was allowed to cool to the room temperature, concentrated under reduced pressure to the 1/4 volume, to which was added 800 ml of water, and extracted twice with 400 ml of ether. The ether layer was washed with 300 ml of water and a saturated aqueous solution of sodium chloride, and the organic layer was dried over magnesium sulfate and filtered. To the filtrate was added 24 g of p-toluenesulfonic acid monohydrate, and stirred for 30 minutes. The precipitate was collected by filtration, and recrystallized from ethyl acetate-edthanol, to give 25.8 g of the title compound.

Workup

  1. temperaturethe mixture was refluxed
  2. temperatureby heating for 3.5 hours
  3. customAfter the reaction the mixture
  4. concentrationconcentrated under reduced pressure to the 1/4 volume, to which
  5. additionwas added 800 ml of water
  6. extractionextracted twice with 400 ml of ether
  7. washThe ether layer was washed with 300 ml of water
  8. dry with materiala saturated aqueous solution of sodium chloride, and the organic layer was dried over magnesium sulfate
  9. filtrationfiltered
  10. additionTo the filtrate was added 24 g of p-toluenesulfonic acid monohydrate
  11. filtrationThe precipitate was collected by filtration
  12. customrecrystallized from ethyl acetate-edthanol

Sources & evidence

ORD record
ord-68c240bcc865426c81f36c8ac8db88b7
Source dataset
uspto-grants-1993_02
Patent number
US05185337

Reaction notes

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