Dichloromethane → 2-Oxo-1-(4-trifluoromethyl-benzyl)-2,3-dihydro-1H-indole-7-carboxylic acid

HRID 1951652Notes

Reaction equation

HRID 1951652 reaction equation
Br[C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:10]=1[N:9]([CH2:11][C:12]1[CH:17]=[CH:16][C:15]([C:18]([F:21])([F:20])[F:19])=[CH:14][CH:13]=1)[C:8](=[O:22])[CH2:7]2.C(Cl)Cl.CCN(CC)CC.CC[O:35][C:36](C)=[O:37]>CS(C)=O.CO.O>[O:22]=[C:8]1[CH2:7][C:6]2[C:10](=[C:2]([C:36]([OH:37])=[O:35])[CH:3]=[CH:4][CH:5]=2)[N:9]1[CH2:11][C:12]1[CH:17]=[CH:16][C:15]([C:18]([F:21])([F:20])[F:19])=[CH:14][CH:13]=1

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 8471TriethylamineHCID 8857Ethyl AcetateHCID 582976787-Bromo-1-(4-trifluoromethylbenzyl)-1,3-dihydro-indol-2-one

Product 1

HCID 582977002-Oxo-1-(4-trifluoromethyl-benzyl)-2,3-dihydro-1H-indole-7-carboxylic acid

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 22036561Dimethyl sulfoxide methanolSolvent

Procedure

A mixture 2.8 g of 7-bromo-1-(4-trifluoromethylbenzyl)-1,3-dihydro-indol-2-one, 0.70 g of PdCl2dppf.CH2Cl2, and 2.34 ml of Et3N in 75 ml of 2:1 DMSO/MeOH was heated under CO (balloon pressure) at 75° C. for 24 h. The reaction mixture was poured into 400 ml of 1:1 heaxan/EtOAc and stirred with 200 ml of water for 4 h. The organic layer was washed with 150 ml of brine and dried over Na2SO4, filtered through a pad of silica gel, and concentrated. The residue was dissolved in 60 ml THF, 20 ml of MeOH and 20 ml of water, followed by 30 ml of 1N aqueous LiOH solution. After stirring for 5 h at room temperature, 5 ml of AcOH was added and the mixture was extracted with 250 ml of EtOAc. The organic layer was washed with 50 ml of brine and dried over Na2SO4, filtered, and concentrated. The residue was swished from 50 ml of 1:1 hexane/EtOAc to give 1.2 g of the title compound as a light brown solid.

Workup

  1. washThe organic layer was washed with 150 ml of brine
  2. dry with materialdried over Na2SO4
  3. filtrationfiltered through a pad of silica gel
  4. concentrationconcentrated
  5. dissolutionThe residue was dissolved in 60 ml THF
  6. addition5 ml of AcOH was added
  7. extractionthe mixture was extracted with 250 ml of EtOAc
  8. washThe organic layer was washed with 50 ml of brine
  9. dry with materialdried over Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-b9dfcc9a1b9e474f8e4465e9589406b0
Source dataset
uspto-grants-2013_03
Patent number
US08404736B2

Reaction notes

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