Citric Acid → 7-[ethyl(2-thienylsulfonyl)amino]-4-methyl-1H-indole-2-carboxylic acid

HRID 1960282Notes

Reaction equation

HRID 1960282 reaction equation
[CH2:1]([N:3]([S:19]([C:22]1[S:23][CH:24]=[CH:25][CH:26]=1)(=[O:21])=[O:20])[C:4]1[CH:5]=[CH:6][C:7]([CH3:18])=[C:8]2[C:12]=1[NH:11][C:10]([C:13]([O:15]CC)=[O:14])=[CH:9]2)[CH3:2].CO.[OH-].[K+].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>O1CCCC1>[CH2:1]([N:3]([S:19]([C:22]1[S:23][CH:24]=[CH:25][CH:26]=1)(=[O:20])=[O:21])[C:4]1[CH:5]=[CH:6][C:7]([CH3:18])=[C:8]2[C:12]=1[NH:11][C:10]([C:13]([OH:15])=[O:14])=[CH:9]2)[CH3:2]

Participants

6

Reactant 4

HCID 311Citric AcidHCID 887MethanolHCID 14797Potassium HydroxideHCID 57476012ethyl 7-[ethyl(2-thienylsulfonyl)amino]-4-methyl-1H-indole-2-carboxylate

Product 1

HCID 574760137-[ethyl(2-thienylsulfonyl)amino]-4-methyl-1H-indole-2-carboxylic acidYield 101.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of ethyl 7-[ethyl(2-thienylsulfonyl)amino]-4-methyl-1H-indole-2-carboxylate (2.12 g) in tetrahydrofuran (15 ml)-methanol (15 ml) was added an aqueous solution (5 ml) of 85% potassium hydroxide (1.0 g), and the mixture was stirred at room temperature for 15 hr. The reaction solution was acidified with aqueous citric acid solution, and extracted with ethyl acetate. The extract was mashed with water and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to give 7-[ethyl(2-thienylsulfonyl)amino]-4-methyl-1H-indole-2-carboxylic acid (2.0 g, yield quantitative) as a colorless amorphous solid. To a mixture of the obtained solid (2.0 g), 1H-1,2,3-benzotriazol-1-ol-ammonia complex (1.0 g) and N,N-dimethylformamide (20 ml) was added N-[3-(dimethylamino)propyl]-N′-ethylcarbodiimide hydrochloride (1.3 g) under ice-cooling, and the mixture was stirred at room temperature for 2 days. The reaction solution was diluted with ethyl acetate, and washed successively with aqueous sodium hydrogencarbonate solution, water and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography (ethyl acetate:hexane=1:1-3:1) to give the title compound (2.0 g, yield quantitative) as a colorless amorphous solid.

Workup

  1. extractionextracted with ethyl acetate
  2. dry with materialdried over anhydrous magnesium sulfate
  3. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-f7691b6ccbc64b92adb9c26c24ff750e
Source dataset
uspto-grants-2013_04
Patent number
US08410087B2

Reaction notes

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