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

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Reaction Steps

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 %.

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