Acetic Anhydride → 2-(ethoxycarbonyl)-1-tosyl-1H-indole-5-carboxylic acid

A mixture of 5-bromo-1-(toluene-4-sulfonyl)-1H-indole-2-carboxylic acid ethyl ester (948.4 mg, 2.24 mmol), Tris(dibenzylideneacetone)dipalladium (0) (0.112 mmol, 103 mg), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (Xantphos) (0.225 mmol, 130 mg), lithium formate monohydrate (5.6 mmol, 394 mg), lithium chloride (286 mg, 6.75 mmol), and anhydrous N,N-dimethylformamide (DMF) (5.9 ml) was evacuated, and backfilled with argon. Then, N,N-diisopropylethyl amine (4.5 mmol, 0.78 ml) and acetic anhydride (4.5 mmol, 0.43 ml) were added to the mixture, and deaeration and argon replacement was performed again. The reaction container was placed in a reaction device preheated at 80° C. and the reaction mixture was stirred for 20 hours. After cooling to room temperature, the reaction mixture was diluted with ethyl acetate and an aqueous solution of 1 M hydrochloric acid, and filtered through Celite. The resulting filtrate was washed with 1 M hydrochloric acid, water, and a saturated aqueous solution of sodium chloride, and then dried over anhydrous sodium sulfate. The desiccant was removed by filtration. The filtrate was concentrated under reduced pressure, and the resulting residue was purified by silica gel column chromatography (hexane/ethyl acetate=5/1 to 1/3, and finally ethyl acetate/methanol=15/1) to give 1-(toluene-4-sulfonyl)-1H-indole-2,5-dicarboxylic acid 2-ethyl ester as a yellow amorphous material (930 mg).

1. customwas evacuated
2. custompreheated at 80° C.
3. filtrationan aqueous solution of 1 M hydrochloric acid, and filtered through Celite
4. washThe resulting filtrate was washed with 1 M hydrochloric acid, water
5. dry with materiala saturated aqueous solution of sodium chloride, and then dried over anhydrous sodium sulfate
6. customThe desiccant was removed by filtration
7. concentrationThe filtrate was concentrated under reduced pressure
8. customthe resulting residue was purified by silica gel column chromatography (hexane/ethyl acetate=5/1 to 1/3, and finally ethyl acetate/methanol=15/1)

ORD 기록

ord-ac0712fed62c440bb652f79476d3e107

출처 데이터셋

uspto-grants-2015_08

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US09102692B2