Water → [4-Acetylamino-3-(4-chlorophenylsulfamyl)-2-methyl-1H-indol-1-yl]acetic acid

HRID 1516985Notes

Reaction equation

HRID 1516985 reaction equation
[C:1]1([N:9](Cl)C(=O)N(Cl)C(=O)N1Cl)=O.[Cl:13][C:14]1[CH:19]=[CH:18]C(SSC2C=CC(Cl)=CC=2)=[CH:16][CH:15]=1.C(OC(=O)CN1C2C(=C(NC(=O)C)C=CC=2)C=C1C)C.C(OC(=O)CN1C2C(=C(N(C(=O)C)C(=O)C)C=CC=2)C=C1C)C.[C:72]([NH:75][C:76]1[CH:84]=[CH:83][CH:82]=[C:81]2[C:77]=1[C:78]([S:92]C1C=CC(Cl)=CC=1)=[C:79]([CH3:91])[N:80]2[CH2:85][C:86]([O:88]CC)=[O:87])(=[O:74])[CH3:73].ClC1C=CC(SC2C3C(=CC=CC=3N(C(=O)C)C(=O)C)N(CC(OCC)=O)C=2C)=CC=1.[OH-:131].[Na+].[OH2:133]>CCOC(C)=O.CCO>[C:72]([NH:75][C:76]1[CH:84]=[CH:83][CH:82]=[C:81]2[C:77]=1[C:78]([S:92](=[O:133])(=[O:131])[NH:9][C:1]1[CH:18]=[CH:19][C:14]([Cl:13])=[CH:15][CH:16]=1)=[C:79]([CH3:91])[N:80]2[CH2:85][C:86]([OH:88])=[O:87])(=[O:74])[CH3:73]

Participants

11

Reactant 8

HCID 962WaterHCID 6909Trichloroisocyanuric AcidHCID 14360Bis(p-chlorophenyl)disulfideHCID 14798Sodium HydroxideHCID 11546184[4-acetylamino-3-(4-chlorophenylsulfanyl)-2-methyl-1H-indol-1-yl]acetic acid ethyl ester2×HCID 58160342ethyl(4-diacetylamino-2-methyl-1H-indol-1-yl)acetateHCID 58160354ethyl[3-(4-chlorophenylsulfanyl)-4-diacetylamino-2-methyl-1H-indol-1-yl]acetate2×HCID 59431286Ethyl 2-(4-acetamido-2-methyl-1H-indol-1-yl)acetate

Product 1

HCID 66937903[4-Acetylamino-3-(4-chlorophenylsulfamyl)-2-methyl-1H-indol-1-yl]acetic acid

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of TCCA (0.326 g, 0.316 g corrected for purity, 1.36 mmol) in EtOAc (10 mL) was added bis(4-chlorophenyl)disulfide (1.18 g, 1.14 g corrected for purity, 4.0 mmol). The solution of ethyl(4-acetylamino-2-methyl-1H-indol-1-yl)acetate and ethyl(4-diacetylamino-2-methyl-1H-indol-1-yl)acetate prepared above was added to the mixture, dropwise, over 10 mins. After stirring for 1 h, the insoluble solid material was removed by filtration. The filtrate was concentrated in vacuo at 40° C. and EtOH (10 mL) was added to the residue to give the product mixture as a solution in EtOH; purity by HPLC: 87.47 area % as a mixture of ethyl [4-acetylamino-3-(4-chlorophenylsulfanyl)-2-methyl-1H-indol-1-yl]acetate and ethyl [3-(4-chlorophenylsulfanyl)-4-diacetylamino-2-methyl-1H-indol-1-yl]acetate; m/z: 417 and 459, both consistent for MH+. A solution of NaOH (0.326 g, 0.319 g corrected for purity, 8.0 mmol) in water (10 mL) was added to the mixture of ethyl [4-acetylamino-3-(4-chlorophenylsulfanyl)-2-methyl-1H-indol-1-yl]acetate and ethyl [3-(4-chlorophenylsulfanyl)-4-diacetylamino-2-methyl-1H-indol-1-yl]acetate in EtOH prepared above. After 2 h, EtOH was removed in vacuo at 35° C. The residual aqueous layer was washed with EtOAc (10 mL), diluted with water (10 mL) then acidified to pH 4 with aqueous hydrochloric acid. The resulting product was collected by filtration then slurried in EtOH (10 mL) at 50° C. for 15 mins. After cooling back to r.t., the solid was collected by filtration, washed with EtOH (4.0 mL) then dried in vacuo at 40° C. to give the title compound as a solid; 1.1 g (35.4% over 3 steps); purity by HPLC: 98.24 area %.

Workup

  1. additionabove was added to the mixture
  2. customthe insoluble solid material was removed by filtration
  3. concentrationThe filtrate was concentrated in vacuo at 40° C.
  4. additionEtOH (10 mL) was added to the residue
  5. customto give the product mixture as a solution in EtOH
  6. customprepared above
  7. waitAfter 2 h
  8. customEtOH was removed in vacuo at 35° C
  9. washThe residual aqueous layer was washed with EtOAc (10 mL)
  10. additiondiluted with water (10 mL)
  11. filtrationThe resulting product was collected by filtration
  12. waitthen slurried in EtOH (10 mL) at 50° C. for 15 mins
  13. filtrationthe solid was collected by filtration
  14. washwashed with EtOH (4.0 mL)
  15. customthen dried in vacuo at 40° C.

Sources & evidence

ORD record
ord-51a21dc07a4040e0b487698a1cd7c5fe
Source dataset
uspto-grants-2012_07
Patent number
US08227622B2

Reaction notes

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