Citric Acid → HCID 67109572, compound

HRID 1851601Notes

Reaction equation

HRID 1851601 reaction equation
[CH2:1]([N:3]([S:20]([C:23]1[S:24][CH:25]=[CH:26][CH:27]=1)(=[O:22])=[O:21])[C:4]1[CH:5]=[C:6]([CH3:19])[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:20]([C:23]1[S:24][CH:25]=[CH:26][CH:27]=1)(=[O:21])=[O:22])[C:4]1[CH:5]=[C:6]([CH3:19])[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 57901725HCID 57901725, compound

Product 1

HCID 67109572HCID 67109572, compoundYield 102.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a mixed solution of ethyl 7-[ethyl(2-thienylsulfonyl)amino]-4,5-dimethyl-1H-indole-2-carboxylate (210 mg) in tetrahydrofuran (8 ml)-methanol (8 mL) was added aqueous solution (5 mL) of 85% potassium hydroxide (100 mg), and the mixture was stirred at room temperature for 6 hr. The reaction solution was acidified with aqueous citric acid solution, extracted with ethyl acetate, washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to give 7-[ethyl(2-thienylsulfonyl)amino]-4,5-dimethyl-1H-indole-2-carboxylic acid (200 mg, yield:quantitative) as colorless crystals. To a mixture of the obtained crystals (200 mg), 1H-1,2,3-benzotriazol-1-ol-ammonia complex (100 mg) and N,N-dimethylformamide (8 mL) was added N-[3-(dimethylamino)propyl]-N′-ethylcarbodiimide hydrochloride (130 mg) under ice-cooling, and the mixture was stirred at room temperature for 2 days. The reaction mixture was diluted with ethyl acetate, 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=2:1) to give the title compound (200 mg, yield: quantitative) as colorless prism crystals.

Workup

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

Sources & evidence

ORD record
ord-408246b2ee58456a884eb786ad27e360
Source dataset
uspto-grants-2015_02
Patent number
US08957070B2

Reaction notes

Loading…