Azobisisobutyronitrile → 2-[(1S)-2-{[4-fluoro-5-(hydroxymethyl)isoxazol-3-yl]oxy}-1-methylethyl]-1H-isoindole-1,3(2H)-dione

HRID 1026265Notes

Reaction equation

HRID 1026265 reaction equation
[F:1][C:2]1[C:3]([O:8][CH2:9][C@@H:10]([N:12]2[C:20](=[O:21])[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[C:13]2=[O:22])[CH3:11])=[N:4][O:5][C:6]=1[CH3:7].BrN1C(=[O:29])CCC1=O.N(C(C)(C)C#N)=NC(C)(C)C#N.FC(C1C=CC=CC=1)(F)F>O>[F:1][C:2]1[C:3]([O:8][CH2:9][C@@H:10]([N:12]2[C:20](=[O:21])[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[C:13]2=[O:22])[CH3:11])=[N:4][O:5][C:6]=1[CH2:7][OH:29]

Participants

6

Reactant 4

HCID 6547AzobisisobutyronitrileHCID 7368(Trifluoromethyl)benzeneHCID 67184N-bromobutanimideHCID 67778378HCID 67778378, compound

Product 1

HCID 677778302-[(1S)-2-{[4-fluoro-5-(hydroxymethyl)isoxazol-3-yl]oxy}-1-methylethyl]-1H-isoindole-1,3(2H)-dioneYield 29.3%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 2-{(1S)-2-[(4-fluoro-5-methylisoxazol-3-yl)oxy]-1-methylethyl}-1H-isoindole-1,3(2H)-dione (383 mg), N-bromosuccinimide (269 mg), 2,2′-azobis(2-methylpropionitrile) (20.7 mg) and (trifluoromethyl)benzene (5 mL) was stirred at 100° C. overnight. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The obtained organic layer was washed with saturated brine, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate). The obtained residue was mixed with 1-methylpyrrolidin-2-one (5 mL) and water (10 mL), and the mixture was stirred at 105° C. overnight. The reaction mixture was extracted with ethyl acetate, and the obtained organic layer was washed with saturated brine, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate) to give the title compound as a colorless oil (118 mg).

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe obtained organic layer was washed with saturated brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. customthe solvent was evaporated under reduced pressure
  5. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate)
  6. additionThe obtained residue was mixed with 1-methylpyrrolidin-2-one (5 mL) and water (10 mL)
  7. stirringthe mixture was stirred at 105° C. overnight
  8. extractionThe reaction mixture was extracted with ethyl acetate
  9. washthe obtained organic layer was washed with saturated brine
  10. dry with materialdried over anhydrous magnesium sulfate
  11. customthe solvent was evaporated under reduced pressure
  12. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate)

Sources & evidence

ORD record
ord-5c7a8aabfef64c41aa30fdf82571fa4f
Source dataset
uspto-grants-2014_05
Patent number
US08729102B2

Reaction notes

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