Citric Acid → ethyl 7-[methyl(2-thienylsulfonyl)amino]-5-(trifluoromethoxy)-1H-indole-2-carboxylate

HRID 1960367Notes

Reaction equation

HRID 1960367 reaction equation
[S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[S:6]([NH:9][C:10]1[CH:11]=[C:12]([O:24][C:25]([F:28])([F:27])[F:26])[CH:13]=[C:14]2[C:18]=1[NH:17][C:16]([C:19]([O:21][CH2:22][CH3:23])=[O:20])=[CH:15]2)(=[O:8])=[O:7].[C:29](=O)([O-])[O-].[K+].[K+].CI.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>CN(C)C=O>[CH3:29][N:9]([S:6]([C:2]1[S:1][CH:5]=[CH:4][CH:3]=1)(=[O:7])=[O:8])[C:10]1[CH:11]=[C:12]([O:24][C:25]([F:27])([F:28])[F:26])[CH:13]=[C:14]2[C:18]=1[NH:17][C:16]([C:19]([O:21][CH2:22][CH3:23])=[O:20])=[CH:15]2

Participants

6

Reactant 4

HCID 311Citric AcidHCID 6328Methyl iodideHCID 11430Potassium CarbonateHCID 57476185ethyl 7-[(2-thienylsulfonyl)amino]-5-(trifluoromethoxy)-1H-indole-2-carboxylate

Product 1

HCID 57476184ethyl 7-[methyl(2-thienylsulfonyl)amino]-5-(trifluoromethoxy)-1H-indole-2-carboxylateYield 66.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

A mixture of ethyl 7-[(2-thienylsulfonyl)amino]-5-(trifluoromethoxy)-1H-indole-2-carboxylate (3.30 g), potassium carbonate (1.05 g) and N,N-dimethylformamide (50 mL) was stirred at 0° C. for 30 min. Methyl iodide (1.08 g) was added to the reaction mixture at 0° C., and the mixture was stirred at room temperature for 15 hr. Aqueous citric acid solution was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine, dried over magnesium sulfate, and concentrated. The obtained residue was subjected to silica gel column chromatography, and eluted with ethyl acetate-hexane (9:1-3:1, volume ratio) to give the title compound (2.26 g, yield 66%) as colorless crystals. The crystals were recrystallized from ethyl acetate-hexane to give colorless prism crystals. melting point 149-150° C.

Workup

  1. stirringthe mixture was stirred at room temperature for 15 hr
  2. extractionthe mixture was extracted with ethyl acetate
  3. washThe ethyl acetate layer was washed with saturated brine
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated
  6. washeluted with ethyl acetate-hexane (9:1-3:1, volume ratio)

Sources & evidence

ORD record
ord-b0dac7e25a2d4e6f86ba9601131ffe54
Source dataset
uspto-grants-2013_04
Patent number
US08410087B2

Reaction notes

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