Iodine → 5-Chloro-3-hydroxy-3-(2-methoxyphenyl)indolin-2-one

HRID 2197431Notes

Reaction equation

HRID 2197431 reaction equation
[Mg].II.Br[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[O:11][CH3:12].[Cl:13][C:14]1[CH:15]=[C:16]2[C:20](=[CH:21][CH:22]=1)[NH:19][C:18](=[O:23])[C:17]2=[O:24].[NH4+].[Cl-]>CCOCC.O>[Cl:13][C:14]1[CH:15]=[C:16]2[C:20](=[CH:21][CH:22]=1)[NH:19][C:18](=[O:23])[C:17]2([OH:24])[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[O:11][CH3:12]

Participants

8

Reactant 5

HCID 807IodineHCID 113582-BromoanisoleHCID 25517Ammonium ChlorideHCID 872035-chloro-1H-indole-2,3-dioneHCID 5462224Magnesium

Product 1

HCID 219059555-Chloro-3-hydroxy-3-(2-methoxyphenyl)indolin-2-one

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 3283Diethyl EtherSolvent2×

Conditions

Temperature
20 °C

Procedure

40 g (1.65 mol) magnesium shavings were overlaid with 100 ml ether, and after the addition of a small amount of iodine, they were carefully heated until the reaction kicked off. 203 ml (1.65 mol) bromanisole, dissolved in 450 ml ether, were dropped in to the boiling solution so slowly that the reaction continually proceeded at a low boil. Subsequently, with slight cooling to 20° C., 75 g (0.41 mol) 5-chlorisatin in 750 ml water-free tetrahydrofurane were added in by drops. After this, everything was stirred for 30 minutes more at room temperature. The reaction solution was poured into an aqueous NH4Cl solution while being stirred. This aqueous phase was extracted a number of times with ethyl acetate and the combined aqueous phases were washed with water four times, dried and concentrated in a vacuum. The residue obtained was crystallised from isopropanol, wherein 106 g of the intermediate product resulted.

Workup

  1. temperaturewere carefully heated until the reaction
  2. additionwere dropped in to the boiling solution so slowly that the reaction
  3. stirringwhile being stirred
  4. extractionThis aqueous phase was extracted a number of times with ethyl acetate
  5. washthe combined aqueous phases were washed with water four times
  6. customdried
  7. concentrationconcentrated in a vacuum
  8. customThe residue obtained
  9. customwas crystallised from isopropanol, wherein 106 g of the intermediate product
  10. customresulted

Sources & evidence

ORD record
ord-7e51d28fdca94e9f9f7e2fae11865cfb
Source dataset
uspto-grants-2012_12
Patent number
US08338590B2

Reaction notes

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