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

HRID 601768

Reaction equation

HRID 601768 reaction equation
[Mg].Br[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[O:9][CH3:10].II.[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].[Cl-].[NH4+]>C(OCC)C.C1COCC1>[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:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[O:9][CH3:10]

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-oneYield 89.2%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolvent2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
21 °C

Procedure

Magnesium turnings (40 g, 1.65 mol) are introduced into diethyl ether (100 ml) and, while stirring, a solution of 2-bromoanisole (206 ml, 1.65 mol) in diethyl ether (450 ml) is added dropwise. The reaction can be initiated, if necessary, by adding iodine crystals. During the addition, the reaction mixture should boil gently. After the addition, the mixture was stirred at room temperature for 1 hour. A slurry of 5-chloroisatin (75 g, 0.41 mol) in THF (750 ml) was added to the Grignard solution while cooling slightly (temperature 18-24° C.), and the mixture was stirred at room temperature for 30 min. The reaction mixture was stirred into ammonium chloride solution and extracted several times with ethyl acetate. The combined organic phase was washed four times with water, dried over magnesium sulfate and concentrated under reduced pressure. The remaining residue was stirred with 2-propanol. The resulting precipitate was filtered off, washed with 2-propanol and diethyl ether and dried. 106 g of the desired intermediate were obtained.

Workup

  1. customThe reaction
  2. additionDuring the addition
  3. additionAfter the addition
  4. stirringthe mixture was stirred at room temperature for 1 hour
  5. stirringthe mixture was stirred at room temperature for 30 min
  6. extractionextracted several times with ethyl acetate
  7. washThe combined organic phase was washed four times with water
  8. dry with materialdried over magnesium sulfate
  9. concentrationconcentrated under reduced pressure
  10. stirringThe remaining residue was stirred with 2-propanol
  11. filtrationThe resulting precipitate was filtered off
  12. washwashed with 2-propanol and diethyl ether
  13. customdried

Sources & evidence

ORD record
ord-d27efc37f2e44cfb8528f7a662d313bd
Source dataset
uspto-grants-2011_03
Patent number
US07902379B2

Linked notes

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