Hydrochloric Acid → Ethyl 1-(benzenesulfonyl)indole-2-carboxylate

HRID 74445Notes

Reaction equation

HRID 74445 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[NH:7][C:8]2[C:13]([CH:14]=1)=[CH:12][CH:11]=[CH:10][CH:9]=2)=[O:5])[CH3:2].[H-].[Na+].[C:17]1([S:23](Cl)(=[O:25])=[O:24])[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.Cl>CN(C)C=O.O>[CH2:1]([O:3][C:4]([C:6]1[N:7]([S:23]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)(=[O:25])=[O:24])[C:8]2[C:13]([CH:14]=1)=[CH:12][CH:11]=[CH:10][CH:9]=2)=[O:5])[CH3:2]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 7369Benzenesulfonyl chlorideHCID 24758Sodium hydrideHCID 73125Ethyl indole-2-carboxylate

Product 1

HCID 506886Ethyl 1-(benzenesulfonyl)indole-2-carboxylateYield 87.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent3×

Procedure

With cooling on ice, an anhydrous N,N-dimethylformamide (DMF) solution (70 ml) of 1H-indole-2-carboxylic acid ethyl ester (45 g, 0.238 mol) was added dropwise to a solution of 50% sodium hydride (13.7 g, 0.286 mol) in anhydrous N,N-dimethylformamide (DMF) (90 ml). After one and half hour of stirring with cooling on ice, the reaction mixture was warmed to room temperature, and then stirred for one hour. After cooling on ice, an anhydrous N,N-dimethylformamide (DMF) solution of benzenesulfonyl chloride (50.4 g) was added dropwise, and the resulting mixture was stirred for one hour. An aqueous solution of 0.5 N hydrochloric acid was added dropwise to the reaction mixture, and then water was added thereto. The mixture was stirred for 30 minutes. The resulting solid was collected by filtration, and washed with water and then with n-hexane. The solid was dissolved in ethyl acetate, and washed with a saturated aqueous solution of sodium bicarbonate and then with a saturated aqueous solution of sodium chloride. The organic layer was dried over anhydrous sodium sulfate. The desiccant was removed by filtration. The filtrate was concentrated under reduced pressure to give crude 1-benzenesulfonyl-1H-indole-2-carboxylic acid ethyl ester. The obtained crude product was recrystallized (ethyl acetate/hexane) to give 1-benzenesulfonyl-1H-indole-2-carboxylic acid ethyl ester (68.9 g, 79%).

Workup

  1. temperatureWith cooling on ice
  2. temperaturewith cooling on ice
  3. stirringstirred for one hour
  4. temperatureAfter cooling on ice
  5. stirringthe resulting mixture was stirred for one hour
  6. stirringThe mixture was stirred for 30 minutes
  7. filtrationThe resulting solid was collected by filtration
  8. washwashed with water
  9. dissolutionThe solid was dissolved in ethyl acetate
  10. washwashed with a saturated aqueous solution of sodium bicarbonate
  11. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  12. customThe desiccant was removed by filtration
  13. concentrationThe filtrate was concentrated under reduced pressure
  14. customto give crude 1-benzenesulfonyl-1H-indole-2-carboxylic acid ethyl ester
  15. customThe obtained crude product
  16. customwas recrystallized (ethyl acetate/hexane)

Sources & evidence

ORD record
ord-a362d06c03734f239bc2fdb374dc3992
Source dataset
uspto-grants-2014_09
Patent number
US08829199B2

Reaction notes

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