Hydrochloric Acid → 5-chloro-3-hydroxy-3-(2-isopropylphenyl)-1,3-dihydro-2H-indol-2-one

HRID 490142Notes

Reaction equation

HRID 490142 reaction equation
Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH:8]([CH3:10])[CH3:9].[Mg].[Cl:12][C:13]1[CH:14]=[C:15]2[C:19](=[CH:20][CH:21]=1)[NH:18][C:17](=[O:22])[C:16]2=[O:23].Cl>O1CCCC1.C(OCC)(=O)C>[Cl:12][C:13]1[CH:14]=[C:15]2[C:19](=[CH:20][CH:21]=1)[NH:18][C:17](=[O:22])[C:16]2([OH:23])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH:8]([CH3:10])[CH3:9]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 23475o-BromocumeneHCID 872035-chloro-1H-indole-2,3-dioneHCID 5462224Magnesium

Product 1

HCID 231207095-chloro-3-hydroxy-3-(2-isopropylphenyl)-1,3-dihydro-2H-indol-2-oneYield 98.3%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent3×HCID 8857Ethyl AcetateSolvent

Procedure

Several drops of a 12 mL tetrahydrofuran solution of 8.2 g of 1-bromo-2-isopropylbenzene were added to a 5 mL tetrahydrofuran solution of 1.2 g of magnesium under a nitrogen atmosphere to initiate the reaction, after which the rest was gradually added drop-wise at a rate at which heating reflux was maintained. Upon completion of the dropping, the reaction mixture was refluxed for 0.5 hour in an oil bath, and then cooled to room temperature. A reagent prepared as above was gradually added drop-wise under ice cooling and a nitrogen atmosphere to a suspension of 3 g of 5-chloro-1H-indol-2,3-dione in 22 mL of tetrahydrofuran. Upon completion of the dropping, the temperature was raised to room temperature, and then the reaction mixture was stirred for 2 hours at that temperature. A 3N hydrochloric acid aqueous solution was poured into the reaction solution, and extraction was performed with ethyl acetate. The organic layer was washed with water and saturated brine and dried with magnesium sulfate, and the drying agent was then filtered off and the solvent was distilled off under reduced pressure. The residue was purified by column chromatography (silica gel 60, mobile phase: ethyl acetate/hexane=1/2; v/v) to obtain 4.9 g of the titled compound (pale yellow, amorphous).

Workup

  1. customthe reaction
  2. temperatureheating
  3. temperaturereflux
  4. temperaturewas maintained
  5. temperatureUpon completion of the dropping, the reaction mixture was refluxed for 0.5 hour in an oil bath
  6. customA reagent prepared
  7. temperatureUpon completion of the dropping, the temperature was raised to room temperature
  8. washThe organic layer was washed with water and saturated brine
  9. dry with materialdried with magnesium sulfate
  10. filtrationthe drying agent was then filtered off
  11. distillationthe solvent was distilled off under reduced pressure
  12. customThe residue was purified by column chromatography (silica gel 60, mobile phase: ethyl acetate/hexane=1/2; v/v)

Sources & evidence

ORD record
ord-a761a052d4384a37a2e7173061f1a3d9
Source dataset
uspto-grants-2009_05
Patent number
US07528124B2

Reaction notes

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