Ethylene Glycol → 2-[(2-Oxo-2,3-dihydro-1H-indol-6-yl)sulfanyl]benzoic acid

HRID 2116787Notes

Reaction equation

HRID 2116787 reaction equation
C(=O)([O-])[O-].[K+].[K+].I[C:8]1[CH:16]=[C:15]2[C:11]([CH2:12][C:13](=[O:17])[NH:14]2)=[CH:10][CH:9]=1.[SH:18][C:19]1[CH:27]=[CH:26][CH:25]=[CH:24][C:20]=1[C:21]([OH:23])=[O:22].C(O)CO.Cl>CCOC(C)=O.O.[Cu]I.CC(O)C>[O:17]=[C:13]1[CH2:12][C:11]2[C:15](=[CH:16][C:8]([S:18][C:19]3[CH:27]=[CH:26][CH:25]=[CH:24][C:20]=3[C:21]([OH:23])=[O:22])=[CH:9][CH:10]=2)[NH:14]1

Participants

10

Reactant 5

HCID 174Ethylene GlycolHCID 313Hydrochloric AcidHCID 54432-Mercaptobenzoic AcidHCID 11430Potassium CarbonateHCID 534188196-Iodo-2-oxindole

Product 1

HCID 587957452-[(2-Oxo-2,3-dihydro-1H-indol-6-yl)sulfanyl]benzoic acidYield 20%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 962WaterSolventHCID 3776IsopropanolSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

CuI (40 mg, 0.05 mmol), potassium carbonate (1.66 g, 12 mmol), 6-iodooxindole (as prepared in Preparation 1; 1.0 g, 4.0 mmol) and 2-mercapto-benzoic acid (0.62 g, 4.0 mmol) were added to a dry schlenk tube. The tube was evacuated and refilled with Ar(g) (3 times). 2-Propanol (5.0 mL) and ethylene glycol (0.5 mL, 8.0 mmol) were injected into the schlenk tube. The schlenk tube was sealed with a teflon valve and was heated to 80° C. and stirred for over 24 hours. Subsequently the reaction mixture was allowed to reach room temperature then diluted with EtOAc (10 mL) and water (10 mL). The mixture was acidified of to a pH=3-4 with the addition of 1 M HCl(aq) and the organics were separated and set aside. The aqueous phase was washed with additional EtOAc (10 mL). The combined organic layers were dried over Na2SO4, filtered and concentrated in vacuo affording a yellow solid. The solid was then purified via flash silica gel chromatography (gradient eluant starting with 5% MeOH in CHCl3 increasing to 10% MeOH in CHCl3) affording the title compound as a pale yellow solid (0.228 g, 0.77 mmol, 20% yield).

Workup

  1. customThe tube was evacuated
  2. additionrefilled with Ar(g) (3 times)
  3. customThe schlenk tube was sealed with a teflon valve
  4. customto reach room temperature
  5. customthe organics were separated
  6. washThe aqueous phase was washed with additional EtOAc (10 mL)
  7. dry with materialThe combined organic layers were dried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customaffording a yellow solid
  11. customThe solid was then purified via flash silica gel chromatography (gradient eluant starting with 5% MeOH in CHCl3 increasing to 10% MeOH in CHCl3)

Sources & evidence

ORD record
ord-c1dca8626e90435b873b16e5d042cd55
Source dataset
uspto-grants-2008_10
Patent number
US07439371B2

Reaction notes

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