Hexane → 5-Chloro-3-hydroxy-3-(2-methoxy-4-triisopropylsilanyloxyphenyl)-1,3-dihydroindol-2-one

HRID 1716794Notes

Reaction equation

HRID 1716794 reaction equation
C([Li])CCC.CCCCCC.Br[C:13]1[CH:29]=[CH:28][C:16]([O:17][Si:18]([CH:25]([CH3:27])[CH3:26])([CH:22]([CH3:24])[CH3:23])[CH:19]([CH3:21])[CH3:20])=[CH:15][C:14]=1[O:30][CH3:31].[Na].[Cl:33][C:34]1[CH:35]=[C:36]2[C:40](=[CH:41][CH:42]=1)[NH:39][C:38](=[O:43])[C:37]2=[O:44].ClC1C=C2C(=CC=1)NC(=O)C2=O.[H-].[Na+].[Cl-].[NH4+]>C1COCC1>[Cl:33][C:34]1[CH:35]=[C:36]2[C:40](=[CH:41][CH:42]=1)[NH:39][C:38](=[O:43])[C:37]2([OH:44])[C:13]1[CH:29]=[CH:28][C:16]([O:17][Si:18]([CH:25]([CH3:27])[CH3:26])([CH:22]([CH3:24])[CH3:23])[CH:19]([CH3:21])[CH3:20])=[CH:15][C:14]=1[O:30][CH3:31]

Participants

9

Reactant 7

HCID 8058HexaneHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 872035-chloro-1H-indole-2,3-dioneHCID 11314363(4-Bromo-3-methoxyphenoxy)triisopropylsilaneHCID 670430655-Chlorisatin sodium saltHCID 178418339Butyllithium

Product 1

HCID 670433315-Chloro-3-hydroxy-3-(2-methoxy-4-triisopropylsilanyloxyphenyl)-1,3-dihydroindol-2-oneYield 41%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of n-butyllithium in hexane (1.6 m, 19.6 ml, 31.4 mmol) was slowly added dropwise to a solution of (4-bromo-3-methoxyphenoxy)triisopropylsilane (8.67 g, 24.1 mmol) in THF (100 ml) at −15° C. After 15 min, a solution of 5-chloroisatin sodium salt [prepared by treating a solution of 5-chloroisatin (3.65 g, 20.1 mmol) in THF with one equivalent of sodium hydride at 0° C. for one h] was added dropwise to the solution of the organolithium species. The reaction mixture was allowed to warm to room temperature and was stirred for a further hour. Aqueous ammonium chloride solution was added to the reaction solution while stirring, and the mixture was extracted 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. Purification by chromatography on silica gel (mobile phase 10-30% gradient of ethyl acetate in dichloromethane) afforded 3.8 g (41%) of the desired adduct.

Workup

  1. stirringwhile stirring
  2. extractionthe mixture was extracted with ethyl acetate
  3. washThe combined organic phase was washed with water and saturated sodium chloride solution
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customPurification by chromatography on silica gel (mobile phase 10-30% gradient of ethyl acetate in dichloromethane)

Sources & evidence

ORD record
ord-552e393f6c8c469c9f3c01b1323803fe
Source dataset
uspto-grants-2010_09
Patent number
US07803834B2

Reaction notes

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