Ammonium Chloride → HCID 67428980, compound

HRID 1662726Notes

Reaction equation

HRID 1662726 reaction equation
C([Li])(C)(C)C.C1(C)C=C(C)C=C(C)C=1Br.[CH3:16][O:17][C:18]1[CH:23]=[CH:22][C:21]([CH3:24])=[CH:20][N:19]=1.C(=O)=O.CC(C)=O.[Cl:32][C:33]1[CH:34]=[C:35]2[C:39](=[CH:40][CH:41]=1)[NH:38][C:37](=[O:42])[C:36]2=[O:43].[NH4+].[Cl-]>C1COCC1.CCOC(C)=O>[Cl:32][C:33]1[CH:34]=[C:35]2[C:39](=[CH:40][CH:41]=1)[NH:38][C:37](=[O:42])[C:36]2([OH:43])[C:23]1[C:18]([O:17][CH3:16])=[N:19][CH:20]=[C:21]([CH3:24])[CH:22]=1

Participants

9

Reactant 6

HCID 25517Ammonium ChlorideHCID 684732-BromomesityleneHCID 872035-chloro-1H-indole-2,3-dioneHCID 3014746Pyridine, 2-methoxy-5-methyl-HCID 18522661Acetone cardiceHCID 178418306HCID 178418306, compound

Product 1

HCID 67428980HCID 67428980, compoundYield 40.7%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

Under nitrogen atmosphere and under dry ice-acetone cooling, tert-butyl lithium (64.0 ml; 1.42 mol/L n-pentane solution) was added to THF (150 ml), then, mesityl bromide (6.57 ml) was added dropwise over 2 minutes. The solution was stirred for one hour under the same conditions. 4.07 g of 2-methoxy-5-methylpyridine was added dropwise to the solution over 3 minutes and then the reaction mixture was stirred under ice cooling for one hour and at room temperature for 30 minutes. The solution was dry ice-acetone-cooled again, a suspension of 3.00 g of 5-chloroisatin in THF (75 ml) was added dropwiseover 2 minutes, then the reaction mixture was warmed to room temperature and was stirred for 18 hours. To the reaction solution was added a saturated aqueous solution of NH4Cl and EtOAc, then liquid separation was performed, the aqueous layer was extracted with EtOAc, the combined organic layer was washed with saturated brine, dried over MgSO4, then, the drying agent was separated by filtration, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by column chromatography (silicagel 60; mobile phase: CHCl3/MeOH/NH4OH=97/3/0.3; v/v/v) to obtain 2.05 g of the title compound (yellow solid).

Workup

  1. stirringthe reaction mixture was stirred under ice cooling for one hour and at room temperature for 30 minutes
  2. temperaturecooled again
  3. additionwas added dropwiseover 2 minutes
  4. stirringwas stirred for 18 hours
  5. customliquid separation
  6. extractionthe aqueous layer was extracted with EtOAc
  7. washthe combined organic layer was washed with saturated brine
  8. dry with materialdried over MgSO4
  9. customthe drying agent was separated by filtration
  10. concentrationthe filtrate was concentrated under reduced pressure
  11. customThe obtained residue was purified by column chromatography (silicagel 60; mobile phase: CHCl3/MeOH/NH4OH=97/3/0.3; v/v/v)

Sources & evidence

ORD record
ord-89c7ec91b156478db935e1920ce46a90
Source dataset
uspto-grants-2011_10
Patent number
US08030499B2

Reaction notes

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