p-Toluidine → (RS)-1-Benzyl-3-hydroxy-3-((4-methylphenyl)aminocarbonylmethyl)indolin-2-one

HRID 1533709Notes

Reaction equation

HRID 1533709 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][CH:3]=1.CCCCCC.C([Li])CCC.[CH2:20]([N:27]1[C:35]2[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=2)[C:29]([CH2:37][C:38](OCC)=[O:39])([OH:36])[C:28]1=[O:43])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1>O1CCCC1.O>[CH2:20]([N:27]1[C:35]2[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=2)[C:29]([OH:36])([CH2:37][C:38]([NH:1][C:2]2[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][CH:3]=2)=[O:39])[C:28]1=[O:43])[C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1

Participants

7

Reactant 4

HCID 7813p-ToluidineHCID 8058HexaneHCID 2645481-Benzyl-3-(ethoxycarbonylmethyl)-3-hydroxyindolin-2-oneHCID 178418339Butyllithium

Product 1

HCID 22013019(RS)-1-Benzyl-3-hydroxy-3-((4-methylphenyl)aminocarbonylmethyl)indolin-2-oneYield 45.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 0.254 g of p-toluidine in 10 ml of dry tetrahydrofuran was added dropwise 1.3 ml of a 1.59M hexane solution of n-butyl lithium at −78° C. under a nitrogen atmosphere, followed by stirring at that temperature for 10 minutes. To the mixture was added a solution of 0.299 g of 1-benzyl-3-(ethoxycarbonylmethyl)-3-hydroxyindolin-2-one in 5 ml of dry tetrahydrofuran at −78° C., followed by stirring at that temperature for 30 minutes. Water was added to the reaction mixture, and the product was extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate and concentrated. The residue was purified by silica gel column chromatography (hexane/ethyl acetate=5/1) to give 0.161 g (44%) of the title compound.

Workup

  1. stirringby stirring at that temperature for 30 minutes
  2. extractionthe product was extracted with chloroform
  3. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  4. concentrationconcentrated
  5. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate=5/1)

Sources & evidence

ORD record
ord-74b39bf76e5d498eabc6811e97159713
Source dataset
uspto-grants-2001_03
Patent number
US06207836B1

Reaction notes

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