4-(三氟甲氧基)-1H-吲哚

反应条件: temp:-5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 0.57 g of sodium cyanoborohydride is gradually added to a solution of 0.87 g of 4-(trifluoromethoxy)indole in 12 ml of trifluoroacetic acid under argon, cooled to a temperature of about −5° C. The reaction mixture is allowed to warm up to 0° C. for 3 hours, and is then poured into 30 g of ice and alkalinized with 21 ml of a concentrated sodium hydroxide solution. After stirring for 19 hours, the mixture is diluted with 60 ml of ethyl acetate and then stirred at ambient temperature for 30 minutes. After settling out, the organic phase is separated and the aqueous phase is extracted with 3×60 ml of ethyl acetate. The organic phases are combined, dried over anhydrous magnesium sulfate, filtered, and then concentrated to dryness under reduced pressure. The residue is treated again with a mixture of 50 ml of water, 50 ml of ethyl acetate and 10 ml of a concentrated sodium hydroxide solution and stirred at ambient temperature for 30 minutes, and then separated by settling out. The organic phase is separated and the aqueous phase is extracted with 3×50 ml of ethyl acetate. The organic phases are combined, dried over anhydrous magnesium sulfate, filtered, and then concentrated to dryness under reduced pressure. The residue is purified by chromatography on a 25 g cartridge of 15-40 μm silica, elution being carried out with 95/5; 90/10; then 85/15 v/v cyclohexane/ethyl acetate mixtures, at a flow rate of 25 ml/min. 0.18 g of impure 4-(trifluoromethoxy)indoline is thus obtained in the form of a yellow oil which is directly used in the next step. to warm up to 0° C. for 3 hours stirred at ambient temperature for 30 minutes the organic phase is separated the aqueous phase is extracted with 3×60 ml of ethyl acetate dried over anhydrous magnesium sulfate filtered concentrated to dryness under reduced pressure The residue is treated again with a mixture of 50 ml of water, 50 ml of ethyl acetate and 10 ml of a concentrated sodium hydroxide solution stirred at ambient temperature for 30 minutes separated The organic phase is separated the aqueous phase is extracted with 3×50 ml of ethyl acetate dried over anhydrous magnesium sulfate filtered concentrated to dryness under reduced pressure The residue is purified by chromatography on a 25 g cartridge of 15-40 μm silica, elution

反应条件: temp:200.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 0.18 g of copper(0) is added to a solution of 1.0 g of 4-(trifluoromethoxy)-1H-indole-2-carboxylic acid in 4.5 ml of quinoline under argon. The reaction mixture is heated at 200° C. for 5 hours, and is then cooled to ambient temperature. After dilution with 30 ml of diethyl ether, the mixture is filtered through Clarcel®. The filtrate is washed successively with 6×10 ml of a 6N hydrochloric acid solution, with 10 ml of a saturated sodium hydrogen carbonate solution and then with 10 ml of saturated brine. The organic phase is dried over anhydrous magnesium sulfate, filtered, and then concentrated to dryness under reduced pressure. The residue is purified by chromatography on a 25 g cartridge of 15-40 μm silica, elution being carried out with a 95/5 v/v cyclohexane/ethyl acetate mixture, at a flow rate of 20 ml/min. 0.33 g of 4-(Trifluoromethoxy)indole is thus obtained in the form of an amber oil, the characteristics of which are the following: is then cooled to ambient temperature After dilution with 30 ml of diethyl ether, the mixture is filtered through Clarcel® The filtrate is washed successively with 6×10 ml of a 6N hydrochloric acid solution, with 10 ml of a saturated sodium hydrogen carbonate solution The organic phase is dried over anhydrous magnesium sulfate filtered concentrated to dryness under reduced pressure The residue is purified by chromatography on a 25 g cartridge of 15-40 μm silica, elution