2-amino-4,5-dichlorophenol

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

実験手順: A 20.87 g. portion of the preceding product (prepared as described above) is stirred in 210 ml. of acetone and 210 ml. of water, then 87.0 g. of sodium dithionite is added portionwise with stirring at room temperature as described in J. Chem. Soc., 4727 (1956). The resulting colorless mixture is heated on a steam bath for 1/2 hour, then is cooled and extracted four times with ether. The ether layer is washed 3 times with brine, then is dried over anhydrous sodium sulfate and evaporated to provide yellow crystals. This material is recrystallized from methylene chloride/hexane to yield 3.63 g. of 2-amino-4,5-dichlorophenol as buff colored crystals. A 4.81 g. amount of this product (prepared as described) is dissolved in 35 ml. of methylene chloride then a 3.51 ml. portion of triethylamine is added and the mixture is stirred. To this is added dropwise with stirring 48 ml. of a solution of 9.90 g. of 4-ethoxy-3-thiophenecarbonyl chloride (prepared as described in Example 1 ) dissolved in 100 ml. of methylene chloride. The mixture is allowed to stir overnight then the precipitate is collected, air dried, triturated with water, collected and dried to yield 4.95 g. of 4',5'-dichloro-4-ethoxy-2'-hydroxy-3-thiophenecarboxanilide. portion of the preceding product (prepared as described above) with stirring at room temperature The resulting colorless mixture is heated on a steam bath for 1/2 hour is cooled extracted four times with ether The ether layer is washed 3 times with brine is dried over anhydrous sodium sulfate evaporated to provide yellow crystals This material is recrystallized from methylene chloride/hexane to yield 3.63 g amount of this product (prepared as described) is dissolved in 35 ml the mixture is stirred To this is added dropwise with stirring 48 ml to stir overnight the precipitate is collected air dried triturated with water collected dried to yield 4.95 g

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

実験手順: To a solution of 2-amino-4,5-dichlorophenol (1.5 g, 8.47 mmol) in THF (20 mL) at 0° C., NaH (60% dispersed in oil, 373 mg, 9.33 mmol) was added and the resulting mixture was stirred for 20 min. To this mixture, 4-chloro-2-fluoropyridine (1.67 g, 12.7 mmol) was added and the resulting mixture was stirred at reflux under argon for 15 h. The mixture was allowed to cool to room temperature and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel (petroleum ether/ethyl acetate=20:1 to 10:1) to afford the desired product (1.1 g, 45% yield). ESI-MS m/z: 287.0 [M−H]−. the resulting mixture was stirred at reflux under argon for 15 h concentrated in vacuo The residue was purified by flash column chromatography on silica gel (petroleum ether/ethyl acetate=20:1 to 10:1)

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

実験手順: To a solution of 2-amino-4,5-dichlorophenol (1.5 g, 8.47 mmol) in THF (20 mL) at 0° C., NaH (60% dispersed in oil, 373 mg, 9.33 mmol) was added and the resulting mixture was stirred for 20 min. To this mixture, 4-chloro-2-fluoropyridine (1.67 g, 12.7 mmol) was added and the resulting mixture was stirred at reflux under argon for 15 h. The mixture was allowed to cool to room temperature and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel (petroleum ether/ethyl acetate=20:1 to 10:1) to afford the desired product (1.1 g, 45% yield). ESI-MS m/z: 287.0 [M−H]−. the resulting mixture was stirred at reflux under argon for 15 h concentrated in vacuo The residue was purified by flash column chromatography on silica gel (petroleum ether/ethyl acetate=20:1 to 10:1)

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

実験手順: To a solution of 2-amino-4,5-dichlorophenol (2.0 g, 11.3 mmol) and ethyl-2-oxoacetate (2.26 g, 12.42 mmol) in DCM (50 mL) at room temperature, AcOH (1 mL) was added and the resulting mixture was stirred for 1 h. To this mixture, NaBH(OAc)3 (7.2 g, 33.9 mmol) was added and then stirred for 16 h. The mixture was concentrated in vacuo and the residue was suspended in DCM. The mixture was filtered through a pad of Celite and the filtrate was washed with brine. The organic layer was dried over anhydrous Na2SO4, filtered and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel (petroleum ether/ethyl acetate=10:1) to afford the desired product (2.4 g, 81% yield) as a solid. stirred for 16 h The mixture was concentrated in vacuo The mixture was filtered through a pad of Celite the filtrate was washed with brine The organic layer was dried over anhydrous Na2SO4 filtered concentrated in vacuo The residue was purified by flash column chromatography on silica gel (petroleum ether/ethyl acetate=10:1)

反応条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred solution of 4,5-dichloro-2-nitrophenol (15 g, 72 mmol) in acetic acid (150 mL) and water (450 mL), iron powder (16 g, 285 mmol) was added in portions. The resulting mixture was stirred at 50° C. for 2 h. The mixture was allowed to cool to room temperature, filtered, and the cake was rinsed with ethyl acetate. The filtrate was extracted with ethyl acetate. The organic layer was washed with water, NaHCO3 (aq.) and brine, dried over Na2SO4 and concentrated in vacuo to afford the desired product (10 g, 78%). to cool to room temperature filtered the cake was rinsed with ethyl acetate The filtrate was extracted with ethyl acetate The organic layer was washed with water, NaHCO3 (aq.) and brine dried over Na2SO4 concentrated in vacuo

反応条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred solution of 4,5-dichloro-2-nitrophenol (15 g, 72 mmol) in acetic acid (150 mL) and water (450 mL), iron powder (16 g, 285 mmol) was added in portions. The resulting mixture was stirred at 50° C. for 2 h. The mixture was allowed to cool to room temperature, filtered, and the cake was rinsed with ethyl acetate. The filtrate was extracted with ethyl acetate. The organic layer was washed with water, NaHCO3 (aq.) and brine, dried over Na2SO4 and concentrated in vacuo to afford the desired product (10 g, 78%). to cool to room temperature filtered the cake was rinsed with ethyl acetate The filtrate was extracted with ethyl acetate The organic layer was washed with water, NaHCO3 (aq.) and brine dried over Na2SO4 concentrated in vacuo

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

実験手順: 6-chloro-2-aminophenol (12B) was prepared from 12A according to the procedure described for preparing 9B in Example 9.

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

実験手順: 106 g of 9A was suspended in 636 ml of water. 233 ml of ammonium hydroxide was added. 239.2 g of sodium dithionite was added over a period of about two hours at such a rate that the temperature of the reaction mixture was kept at about 50° C. The mixture was stirred at room temperature for two hours. The solid product was filtered, and extracted with methanol. Evaporation of the solvent from the extract gave 3,4-dichloro-6-aminophenol (9B). was kept at about 50° C The solid product was filtered extracted with methanol Evaporation of the solvent from the extract

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

実験手順: A 20.87 g. portion of the preceding product (prepared as described above) is stirred in 210 ml. of acetone and 210 ml. of water, then 87.0 g. of sodium dithionite is added portionwise with stirring at room temperature as described in J. Chem. Soc., 4727 (1956). The resulting colorless mixture is heated on a steam bath for 1/2 hour, then is cooled and extracted four times with ether. The ether layer is washed 3 times with brine, then is dried over anhydrous sodium sulfate and evaporated to provide yellow crystals. This material is recrystallized from methylene chloride/hexane to yield 3.63 g. of 2-amino-4,5-dichlorophenol as buff colored crystals. A 4.81 g. amount of this product (prepared as described) is dissolved in 35 ml. of methylene chloride then a 3.51 ml. portion of triethylamine is added and the mixture is stirred. To this is added dropwise with stirring 48 ml. of a solution of 9.90 g. of 4-ethoxy-3-thiophenecarbonyl chloride (prepared as described in Example 1 ) dissolved in 100 ml. of methylene chloride. The mixture is allowed to stir overnight then the precipitate is collected, air dried, triturated with water, collected and dried to yield 4.95 g. of 4',5'-dichloro-4-ethoxy-2'-hydroxy-3-thiophenecarboxanilide. portion of the preceding product (prepared as described above) with stirring at room temperature The resulting colorless mixture is heated on a steam bath for 1/2 hour is cooled extracted four times with ether The ether layer is washed 3 times with brine is dried over anhydrous sodium sulfate evaporated to provide yellow crystals This material is recrystallized from methylene chloride/hexane to yield 3.63 g amount of this product (prepared as described) is dissolved in 35 ml the mixture is stirred To this is added dropwise with stirring 48 ml to stir overnight the precipitate is collected air dried triturated with water collected dried to yield 4.95 g

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

実験手順: To a solution of 2-amino-4,5-dichlorophenol (1.5 g, 8.47 mmol) in THF (20 mL) at 0° C., NaH (60% dispersed in oil, 373 mg, 9.33 mmol) was added and the resulting mixture was stirred for 20 min. To this mixture, 4-chloro-2-fluoropyridine (1.67 g, 12.7 mmol) was added and the resulting mixture was stirred at reflux under argon for 15 h. The mixture was allowed to cool to room temperature and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel (petroleum ether/ethyl acetate=20:1 to 10:1) to afford the desired product (1.1 g, 45% yield). ESI-MS m/z: 287.0 [M−H]−. the resulting mixture was stirred at reflux under argon for 15 h concentrated in vacuo The residue was purified by flash column chromatography on silica gel (petroleum ether/ethyl acetate=20:1 to 10:1)

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

実験手順: To a solution of 2-amino-4,5-dichlorophenol (2.0 g, 11.3 mmol) and ethyl-2-oxoacetate (2.26 g, 12.42 mmol) in DCM (50 mL) at room temperature, AcOH (1 mL) was added and the resulting mixture was stirred for 1 h. To this mixture, NaBH(OAc)3 (7.2 g, 33.9 mmol) was added and then stirred for 16 h. The mixture was concentrated in vacuo and the residue was suspended in DCM. The mixture was filtered through a pad of Celite and the filtrate was washed with brine. The organic layer was dried over anhydrous Na2SO4, filtered and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel (petroleum ether/ethyl acetate=10:1) to afford the desired product (2.4 g, 81% yield) as a solid. stirred for 16 h The mixture was concentrated in vacuo The mixture was filtered through a pad of Celite the filtrate was washed with brine The organic layer was dried over anhydrous Na2SO4 filtered concentrated in vacuo The residue was purified by flash column chromatography on silica gel (petroleum ether/ethyl acetate=10:1)

反応条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred solution of 4,5-dichloro-2-nitrophenol (15 g, 72 mmol) in acetic acid (150 mL) and water (450 mL), iron powder (16 g, 285 mmol) was added in portions. The resulting mixture was stirred at 50° C. for 2 h. The mixture was allowed to cool to room temperature, filtered, and the cake was rinsed with ethyl acetate. The filtrate was extracted with ethyl acetate. The organic layer was washed with water, NaHCO3 (aq.) and brine, dried over Na2SO4 and concentrated in vacuo to afford the desired product (10 g, 78%). to cool to room temperature filtered the cake was rinsed with ethyl acetate The filtrate was extracted with ethyl acetate The organic layer was washed with water, NaHCO3 (aq.) and brine dried over Na2SO4 concentrated in vacuo