Methyl iodide → 3-(N-Acetyl-n-methylamino)-2-benzoyl-6-chloroindole

HRID 379848Notes

Reaction equation

HRID 379848 reaction equation
[C:1]([NH:4][C:5]1[C:13]2[C:8](=[CH:9][C:10]([Cl:14])=[CH:11][CH:12]=2)[N:7](C(OCC)=O)[C:6]=1[C:20](=[O:27])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)(=[O:3])[CH3:2].[H-].[Na+].I[CH3:31].[OH-].[K+]>CN(C)C=O.O>[C:1]([N:4]([C:5]1[C:13]2[C:8](=[CH:9][C:10]([Cl:14])=[CH:11][CH:12]=2)[NH:7][C:6]=1[C:20](=[O:27])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[CH3:31])(=[O:3])[CH3:2]

Participants

7

Reactant 4

HCID 6328Methyl iodideHCID 14797Potassium HydroxideHCID 24758Sodium hydrideHCID 183680413-Acetylamino-2-benzoyl-6-chloro-1-(ethoxycarbonyl)indole

Product 1

HCID 183679953-(N-Acetyl-n-methylamino)-2-benzoyl-6-chloroindoleYield 63%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 3-acetylamino-2-benzoyl-6-chloro-1-(ethoxycarbonyl)indole (Example 2, step 1, 900 mg, 2.34 mmol) in dimethylformamide (10 ml) was added sodium hydride (60% w/w dispersion in mineral oil, 94 mg, 2.34 mmol). The mixture was stirred for 0.5 h and then iodomethane (0.22 ml, 3.51 mmol) was added dropwise, and stirring continued for 19 h. The reaction mixture was poured into water (50 ml) and extracted with diethyl ether (100 ml×2). The extracts were washed consecutively with water (50 ml) and brine (50 ml), dried (MgSO4) and solvent removed by evaporation. The residual oil was dissolved in ethanol/water (1:1, 20 ml) and KOH (85% pellets, 264 mg, 4.0 mmol) added. After stirring for 3 h, the mixture was concentrated and the residue partitioned between water (100 ml) and diethyl ether (100 ml). The organic layer was separated and washed consecutively with water (100 ml) and brine (100 m), dried (MgSO4) and solvent removed by evaporation. The residual solids were recrystallized from dichloromethane/hexane to afford 165 mg (63%) of the title compound as a yellow powder. m.p.: 232-235° C.

Workup

  1. stirringstirring
  2. waitcontinued for 19 h
  3. extractionextracted with diethyl ether (100 ml×2)
  4. washThe extracts were washed consecutively with water (50 ml) and brine (50 ml)
  5. dry with materialdried (MgSO4) and solvent
  6. customremoved by evaporation
  7. dissolutionThe residual oil was dissolved in ethanol/water (1:1, 20 ml)
  8. stirringAfter stirring for 3 h
  9. concentrationthe mixture was concentrated
  10. customthe residue partitioned between water (100 ml) and diethyl ether (100 ml)
  11. customThe organic layer was separated
  12. washwashed consecutively with water (100 ml) and brine (100 m)
  13. dry with materialdried (MgSO4) and solvent
  14. customremoved by evaporation
  15. customThe residual solids were recrystallized from dichloromethane/hexane

Sources & evidence

ORD record
ord-c8351edd45a54edf86bc9148d73b376f
Source dataset
uspto-grants-2001_10
Patent number
US06300363B1

Reaction notes

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