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

HRID 1469595Notes

Reaction equation

HRID 1469595 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 shavings (2.2 g, 89 mmol) were placed in THF (30 mL) and etched with several iodine crystals. A solution of 2-(3-bromo-4-methoxyphenyl)-5,5-dimethyl[1,3]dioxane (26.0 g, 86 mmol) in THF (80 mL) was added thereto, with stirring. After initiation of the reaction (identifiable by the exothermic evolution of heat), the rate of dropwise addition was decreased so that the reaction mixture was just at the boiling point. The reaction mixture was stirred for an additional 20 min and then was cooled to room temperature. The Grignard solution thus obtained was pumped into an ice-cold solution of the 5-chlorisatin sodium salt (prepared by treating a solution of 5-chlorisatin (13.1 g, 72 mmol) in THF (400 mL) with one equivalent of sodium hydride for one hour at 0° C.), and was then stirred for 5 hours at room temperature. The reaction solution was combined with aqueous ammonium chloride solution, with stirring, and the batch 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. Treatment of the residue with diethyl ether resulted in crystallization of the desired product. Yield: 19.2 g (66%) of a white solid. MS (API-ES, pos) m/z=386 [M+H—H2O]+.

Workup

  1. customAfter initiation of the reaction (identifiable by the exothermic evolution
  2. temperatureof heat),
  3. additionthe rate of dropwise addition
  4. stirringThe reaction mixture was stirred for an additional 20 min
  5. customThe Grignard solution thus obtained
  6. customprepared
  7. stirringwas then stirred for 5 hours at room temperature
  8. stirringwith stirring
  9. extractionthe batch was extracted twice with ethyl acetate
  10. washThe combined organic phase was washed with water and saturated sodium chloride solution
  11. dry with materialdried over magnesium sulfate
  12. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-1fdd39f08bb84be699fec0706f9f4817
Source dataset
uspto-grants-2015_04
Patent number
US09006276B2

Reaction notes

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