Oxalyl chloride → 1H-Indole-3-carbonyl chloride

1H-indole-3-carboxylic acid (3.00 g, 18.6 mmol) was suspended in 1,2-dichloroethane (15 mL), and oxalyl chloride (2.42 mL, 25.38 mmol) was added dropwise. To this reaction liquor, a catalytic amount of DMF (one drop) was added, and the reaction liquor was stirred for one hour at room temperature. The solvent of the reaction mixture was distilled off under reduced pressure, to obtain 1H-indole-3-carboxylic acid chloride as a solid. The obtained acid chloride was suspended in 1,2-dichloroethane (20 mL), and (4-amino-2,5-dichlorophenyl)acetic acid ethyl ester hydrochloride (4.82 g, 16.92 mmol) was added thereto. The mixture was heated to ref lux for 18 hours with stirring. The reaction mixture was left to cool naturally to room temperature, and then the solvent was distilled off under reduced pressure. The obtained solids were dissolved in chloroform (100 mL), washed with a saturated aqueous solution of sodium hydrogen carbonate and water, and dried over anhydrous sodium sulfate, and then the solvent was distilled off under reduced pressure. The obtained solids were collected by filtration using hexane, to obtain [2,5-d]chloro-4-[(1H-indol-3-ylcarbonyl)amino]phenyl]acetic acid ethyl ester (5.95 g, 90%) as a solid. This compound was used in the subsequent reaction without performing further purification.

1. distillationThe solvent of the reaction mixture was distilled off under reduced pressure

ORD record

ord-d02a0fdfe1964f9e8f1b003dbf345f33

Source dataset

uspto-grants-2012_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08129366B2