Diethyl Ether → ethyl 4,5-dichloro-1H-indole-2-carboxylate

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Reaction Steps

The title compound was prepared according to the general procedure of Scheme 2. A mixture of 3,4-dichlorophenylhydrazine (5.0 g) in benzene (50 mL) was treated sequentially with ethylpyruvate (2.6 mL) and p-toluenesulfonic acid (trace). The mixture was heated at reflux temperature (Dean and Stark conditions) for 5 h then cooled to ambient temperature to afford a solution of 2-[(3,4-dichloro-phenyl)-hydrazono]-propionic acid ethyl ester. Separately a solution of p-toluenesulfonic acid (15 g) in benzene (150 mL) was heated at reflux temperature (Dean and Stark conditions) for 2 h and then treated with the hydrazone solution. After 3 h the reaction mixture was cooled, treated with saturated sodium hydrogen carbonate solution and diethyl ether. The organic fraction was separated, washed with saturated sodium hydrogen carbonate solution and then brine, dried over magnesium sulfate and filtered, and solvent was evaporated to give an orange solid. The solid was purified via silica gel chromatography (15-75% ethylacetate/hexane) to afford 4,5-Dichloro-1H-indole-2-carboxylic acid ethyl ester (0.5 g, 8%) and 5,6-Dichloro-1H-indole-2-carboxylic acid ethyl ester (0.297 g, 5%). These materials were used separately without further purification.

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