Benzoyl Peroxide → 5-Bromo-2-(2,2-difluoroethyl)-2,3-dihydro-1H-isoindol-1-one

HRID 1893576Notes

Reaction equation

HRID 1893576 reaction equation
C(O[C:4](=[O:13])[C:5]1[CH:10]=[CH:9][C:8]([Br:11])=[CH:7][C:6]=1[CH3:12])C.BrN1C(=O)CCC1=O.C(OOC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1.[F:40][CH:41]([F:44])[CH2:42][NH2:43].C(N(CC)CC)C>CCCCCC.C(OCC)(=O)C.CCCCCC.C(Cl)(Cl)(Cl)Cl>[Br:11][C:8]1[CH:7]=[C:6]2[C:5](=[CH:10][CH:9]=1)[C:4](=[O:13])[N:43]([CH2:42][CH:41]([F:44])[F:40])[CH2:12]2

Participants

9

Reactant 5

HCID 7187Benzoyl PeroxideHCID 8471TriethylamineHCID 67184N-bromobutanimideHCID 1362742,2-DifluoroethanamineHCID 22616358Ethyl 4-bromo-2-methylbenzoate

Product 1

HCID 231581115-Bromo-2-(2,2-difluoroethyl)-2,3-dihydro-1H-isoindol-1-oneYield 49%

Reagents, catalysts & solvents 3

HCID 5943Carbon TetrachlorideSolventHCID 8058HexaneSolventHCID 21226206Ethyl acetate hexaneSolvent

Procedure

To carbon tetrachloride (160 ml) were added the compound (10.5 g, 43.2 mmol) of step A, N-bromosuccinimide (8.08 g, 45.4 mmol) and benzoyl peroxide (724 mg), and the mixture was heated under reflux for 50 min. The reaction mixture was cooled and diluted with hexane, the insoluble material was filtered off, and the obtained solution was concentrated under reduced pressure. The obtained oil (18.0 g) was dissolved in N,N-dimethylformamide (180 ml), 2,2-difluoroethylamine (5.99 g, 73.9 mmol) and triethylamine (12.0 ml, 86.1 mmol) were added, and the mixture was stirred at room temperature for 14 hr. The reaction mixture was diluted with an ethyl acetate-hexane=1:1 mixed solvent, washed with water, 10% aqueous citric acid solution, saturated aqueous sodium hydrogen carbonate and saturated brine, and dried over anhydrous magnesium sulfate. The insoluble material was filtered off, and the solution was concentrated under reduced pressure. The obtained oil was purified by silica gel column chromatography (ethyl acetate-hexane) to give the title compound (5.80 g, yield 49%) as a colorless oil.

Workup

  1. temperaturethe mixture was heated
  2. temperatureunder reflux for 50 min
  3. temperatureThe reaction mixture was cooled
  4. filtrationthe insoluble material was filtered off
  5. concentrationthe obtained solution was concentrated under reduced pressure
  6. dissolutionThe obtained oil (18.0 g) was dissolved in N,N-dimethylformamide (180 ml)
  7. washwashed with water, 10% aqueous citric acid solution, saturated aqueous sodium hydrogen carbonate and saturated brine
  8. dry with materialdried over anhydrous magnesium sulfate
  9. filtrationThe insoluble material was filtered off
  10. concentrationthe solution was concentrated under reduced pressure
  11. customThe obtained oil was purified by silica gel column chromatography (ethyl acetate-hexane)

Sources & evidence

ORD record
ord-538988f1651a4fc4879bc67c795cc55e
Source dataset
uspto-grants-2013_08
Patent number
US08513235B2

Reaction notes

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