1-Methoxy-2-propanol → 7-(2-Methoxy-1-methylethoxy)-5-{[6-(methylsulfonyl)pyridin-3-yl]oxy}-1H-indole-2-carboxylic acid

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Reaction Conditions

Reaction Steps

To a solution of methyl 7-hydroxy-5-{[6-(methylsulfonyl)pyridin-3-yl]oxy}-1H-indole-2-carboxylate (2.5 g), tributylphosphine (2.79 g) and 1-methoxypropan-2-ol (1.24 g) in tetrahydrofuran (50 mL) was added 1,1′-(azodicarbonyl)dipiperidine (3.48 g) at 60° C. The whole was stirred at 60° C. for 1.5 h and then concentrated in vacuo. Diisopropyl ether was added to the residue and insoluble materials were removed by filtration. The filtrate was concentrated in vacuo. The residue was purified by silica gel chromatography (ethyl acetate:hexane=1:2 to 2:1, volume ratio) and then by basic silica gel chromatography (ethyl acetate:hexane=1:2 to 2:1, volume ratio) to give a colorless oil. A mixture of the oil, 1M aqueous sodium hydroxide solution (15 mL), tetrahydrofuran (15 mL) and methanol (15 mL) was stirred at room temperature for 20 h. The mixture was washed with diethyl ether. The organic layer was extracted with 1M aqueous sodium hydroxide solution. The water layers were combined, acidified by 1M hydrochloric acid, and extracted with ethyl acetate. The organic layer was washed with brine, dried (MgSO4), filtered, and concentrated in vacuo. The residue was washed with hexane to give the title compound (1.50 g, 52%) as colorless crystals. MS 421 (MH+).

Provenance & Evidence