反应详情

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 %.

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.