Iodine → 5-Chloro-3-[5-(5,5-dimethyl-[1,3]dioxan-2-yl)-2-methoxyphenyl]-3-hydroxy-1,3-dihydroindol-2-one

HRID 2361841Notes

Reaction equation

HRID 2361841 reaction equation
[Mg].II.Br[C:5]1[CH:6]=[C:7]([CH:13]2[O:18][CH2:17][C:16]([CH3:20])([CH3:19])[CH2:15][O:14]2)[CH:8]=[CH:9][C:10]=1[O:11][CH3:12].[Na].[Cl:22][C:23]1[CH:24]=[C:25]2[C:29](=[CH:30][CH:31]=1)[NH:28][C:27](=[O:32])[C:26]2=[O:33].ClC1C=C2C(=CC=1)NC(=O)C2=O.[H-].[Na+].[Cl-].[NH4+]>C1COCC1>[Cl:22][C:23]1[CH:24]=[C:25]2[C:29](=[CH:30][CH:31]=1)[NH:28][C:27](=[O:32])[C:26]2([C:5]1[CH:6]=[C:7]([CH:13]2[O:18][CH2:17][C:16]([CH3:20])([CH3:19])[CH2:15][O:14]2)[CH:8]=[CH:9][C:10]=1[O:11][CH3:12])[OH:33]

Participants

9

Reactant 7

HCID 807IodineHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 872035-chloro-1H-indole-2,3-dioneHCID 8494352-(3-Bromo-4-methoxyphenyl)-5,5-dimethyl-1,3-dioxaneHCID 5462224MagnesiumHCID 670430655-Chlorisatin sodium salt

Product 1

HCID 670429795-Chloro-3-[5-(5,5-dimethyl-[1,3]dioxan-2-yl)-2-methoxyphenyl]-3-hydroxy-1,3-dihydroindol-2-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

Magnesium turnings (2.2 g, 89 mmol) were introduced into THF (30 ml) and etched with some iodine crystals. While stirring, a solution of 2-(3-bromo-4-methoxy-phenyl)-5,5-dimethyl-[1,3]dioxane (26.0 g, 86 mmol) in THF (80 ml) was added thereto. After the reaction started (identifiable by the evolution of heat), the rate of dropwise addition was slowed down so that the reaction mixture just continued to boil. The reaction mixture was then stirred for 20 min and subsequently cooled to room temperature. The Grignard solution obtained in this way was pumped into an ice-cooled solution of 5-chloroisatin sodium salt [prepared by treating a solution of 5-chloroisatin (13.1 g, 72 mmol) in THF (400 ml) with one equivalent of sodium hydride at 0° C. for one h] and then stirred at room temperature for 5 hours. Aqueous ammonium chloride solution was added to the reaction solution while stirring, and the mixture was extracted twice with ethyl acetate. The combined organic phase was washed with water and saturated sodium chloride solution, dried over magnesium sulfate and concentrated under reduced pressure. The desired product crystallizes on treating the residue with diethyl ether. Yield: 19.2 g (66%) of a white solid. MS (API-ES, pos) m/z=386 [M+H—H2O]+

Workup

  1. temperatureof heat),
  2. additionthe rate of dropwise addition
  3. stirringThe reaction mixture was then stirred for 20 min
  4. customThe Grignard solution obtained in this way
  5. customprepared
  6. stirringthen stirred at room temperature for 5 hours
  7. stirringwhile stirring
  8. extractionthe mixture was extracted twice with ethyl acetate
  9. washThe combined organic phase was washed with water and saturated sodium chloride solution
  10. dry with materialdried over magnesium sulfate
  11. concentrationconcentrated under reduced pressure
  12. customThe desired product crystallizes
  13. additionon treating the residue with diethyl ether

Sources & evidence

ORD record
ord-791e092b39dc4ec8917e3237cbaf21a3
Source dataset
uspto-grants-2014_04
Patent number
US08691815B2

Reaction notes

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