Hydrochloric Acid → 7-[[(2-methoxyphenyl)sulfonyl](methyl)amino]-1H-indole-2-carboxylic acid

Temperature

90 °C

A mixture of ethyl 1-(methoxymethyl)-7-[[(2-methoxyphenyl)sulfonyl](methyl)amino]-1H-indole-2-carboxylate (10.9 g), 6N-hydrochloric acid (50 mL), tetrahydrofuran (50 mL) and methanol (50 mL) was stirred at 90° C. for 24 hr. The organic solvent of the reaction solution was evaporated under reduced pressure, and the residue was diluted with ethyl acetate. The solution was washed with water and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The obtained residue was dissolved in a mixed solvent of tetrahydrofuran (50 mL)-methanol (50 mL), aqueous potassium hydroxide solution (prepared by dissolving potassium hydroxide (4.2 g) in water (30 mL)) was added to this solution, and the mixture was stirred at room temperature for 15 hr. The reaction solution was acidified with aqueous citric acid solution, and extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The obtained pale-brown crystals were filtered off, and washed with ethyl acetate-hexane. The filtrate was concentrated under reduced pressure; and the obtained crystals were washed with ethyl acetate-hexane to give the title compound (6.47 g, crude yield: 71%) as pale-yellow crystals. MS: 361(MH+).

1. customThe organic solvent of the reaction solution was evaporated under reduced pressure
2. additionthe residue was diluted with ethyl acetate
3. washThe solution was washed with water and saturated brine
4. dry with materialdried over anhydrous magnesium sulfate
5. concentrationconcentrated under reduced pressure
6. dissolutionThe obtained residue was dissolved in a mixed solvent of tetrahydrofuran (50 mL)-methanol (50 mL), aqueous potassium hydroxide solution (prepared by dissolving potassium hydroxide (4.2 g) in water (30 mL))
7. additionwas added to this solution
8. stirringthe mixture was stirred at room temperature for 15 hr
9. extractionextracted with ethyl acetate
10. washThe organic layer was washed with saturated brine
11. dry with materialdried over anhydrous magnesium sulfate
12. concentrationconcentrated under reduced pressure
13. filtrationThe obtained pale-brown crystals were filtered off
14. washwashed with ethyl acetate-hexane
15. concentrationThe filtrate was concentrated under reduced pressure
16. washand the obtained crystals were washed with ethyl acetate-hexane

ORD record

ord-4ad9a7f844674849868d1deb59e950e7

Source dataset

uspto-grants-2013_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08410087B2