5,7-DICHLORO-1H-INDOLE-2-CARBOXYLIC ACID ETHYL ESTER

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 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. at reflux temperature (Dean and Stark conditions) for 2 h After 3 h the reaction mixture was cooled The organic fraction was separated washed with saturated sodium hydrogen carbonate solution brine, dried over magnesium sulfate filtered solvent was evaporated to give an orange solid The solid was purified via silica gel chromatography (15-75% ethylacetate/hexane)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 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. at reflux temperature (Dean and Stark conditions) for 2 h After 3 h the reaction mixture was cooled The organic fraction was separated washed with saturated sodium hydrogen carbonate solution brine, dried over magnesium sulfate filtered solvent was evaporated to give an orange solid The solid was purified via silica gel chromatography (15-75% ethylacetate/hexane)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 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. at reflux temperature (Dean and Stark conditions) for 2 h After 3 h the reaction mixture was cooled The organic fraction was separated washed with saturated sodium hydrogen carbonate solution brine, dried over magnesium sulfate filtered solvent was evaporated to give an orange solid The solid was purified via silica gel chromatography (15-75% ethylacetate/hexane)

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Ethyl 5,6-dichloro-1H-indole-2-carboxylate (77.5 g, 301 mmol) dissolved in dry THF (70 ml) was added dropwise to an ice cold solution of LiAlH4 (19.17 g, 505 mmol) in anhydrous THF (1000 ml) under nitrogen. The mixture was stirred for 45 min at 0° C. and then quenched by the sequential addition of water (20 ml), 15% aqueous NaOH (20 ml) and water (60 ml). The mixture was filtered through-a Celite pad and then washed with THF (2×500 ml). The filtrate dried over Na2SO4 and evaporated at reduced pressure yielded an orange raw solid. This was dissolved in CH2Cl2 (1500 ml) and activated MnO2 (150 g, 1.73 mol) was added. The mixture was stirred at RT for 12 hours and then filtered through a Celite pad which was washed with warm acetone (4×750 ml), and the combined filtrates were evaporated to dryness, yielding pure title compound (42.1 g, 197 mmol, yield 65.4%), mp=207-208° C. quenched by the sequential addition of water (20 ml), 15% aqueous NaOH (20 ml) and water (60 ml) The mixture was filtered through-a Celite pad washed with THF (2×500 ml) The filtrate dried over Na2SO4 evaporated at reduced pressure yielded an orange raw solid The mixture was stirred at RT for 12 hours filtered through a Celite pad which was washed with warm acetone (4×750 ml) the combined filtrates were evaporated to dryness

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of ethyl α-oxo-3-(2-nitro-4,5-dichlorophenyl)propanoate (100 g, 327 mmol) and iron powder (160 g) in EtOH (625 ml) and acetic acid (625 ml) was refluxed for two hours. After cooling, the resulting mixture was evaporated under vacuum and the solid residue was dissolved in THF (1000 ml) and chromatographed on Florisil (500 g) eluting with THF (5000 ml). Evaporation of the collected fractions gave pure title compound (77.5 g, 301 mmol, yield 92.0%) as a light brown powder, m.p. 215°-218° C. was refluxed for two hours After cooling the resulting mixture was evaporated under vacuum the solid residue was dissolved in THF (1000 ml) chromatographed on Florisil (500 g) eluting with THF (5000 ml) Evaporation of the collected fractions

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 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. at reflux temperature (Dean and Stark conditions) for 2 h After 3 h the reaction mixture was cooled The organic fraction was separated washed with saturated sodium hydrogen carbonate solution brine, dried over magnesium sulfate filtered solvent was evaporated to give an orange solid The solid was purified via silica gel chromatography (15-75% ethylacetate/hexane)