3,4-difluoro-2-methoxyaniline

反応条件: temp:0.00; pressure:0.00; stir:

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

実験手順: 2.84 g (0.013 mole) of diethyl ethoxymethylenemalonate were added to 1.74 g (0.011 mole) of 3,4-difluoro-2-methoxyaniline (VIII) (prepared as described in Preparation 13). The mixture was then stirred at 140°-150° C. for 3 hours, after which 20 ml of diphenyl ether were added, and the mixture was stirred at 240°-250° C. for 1 hour. At the end of this time, the mixture was allowed to cool to room temperature, and then hexane was added to precipitate crystals, which were collected by filtration. 1.60 g of ethyl 6,7-difluoro-4-hydroxy-8-methoxyquinoline-3-carboxylate (IX) were obtained as colorless crystals. the mixture was stirred at 240°-250° C. for 1 hour to precipitate crystals, which were collected by filtration

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

実験手順: 22.6 g (0.422 mole) of ammonium chloride and 38.2 g of reduced iron were added to a solution of 23.0 g (0.114 mole) of 3,4-difluoro-2-methoxy-1-nitrobenzene (VII) [prepared as described in step (a) above] in 1 liter of 80% aqueous methanol. The mixture was then heated under reflux for 4 hours, whilst stirring. At the end of this time, the reaction mixture was filtered, and the filtrate was concentrated by evaporation under reduced pressure. The residue was extracted with toluene. The toluene extract was washed with water, dried, and concentrated by evaporation under reduced pressure to give 10.2 g of 3,4-difluoro-2-methoxyaniline (VIII) as a reddish-brown oil [Step (B2)]. The mixture was then heated under reflux for 4 hours At the end of this time, the reaction mixture was filtered the filtrate was concentrated by evaporation under reduced pressure The residue was extracted with toluene The toluene extract was washed with water dried concentrated by evaporation under reduced pressure

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

実験手順: 2.84 g (0.013 mole) of diethyl ethoxymethylenemalonate were added to 1.74 g (0.011 mole) of 3,4-difluoro-2-methoxyaniline (VIII) (prepared as described in Preparation 13). The mixture was then stirred at 140°-150° C. for 3 hours, after which 20 ml of diphenyl ether were added, and the mixture was stirred at 240°-250° C. for 1 hour. At the end of this time, the mixture was allowed to cool to room temperature, and then hexane was added to precipitate crystals, which were collected by filtration. 1.60 g of ethyl 6,7-difluoro-4-hydroxy-8-methoxyquinoline-3-carboxylate (IX) were obtained as colorless crystals. the mixture was stirred at 240°-250° C. for 1 hour to precipitate crystals, which were collected by filtration

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

実験手順: 2.84 g (0.013 mole) of diethyl ethoxymethylenemalonate were added to 1.74 g (0.011 mole) of 3,4-difluoro-2-methoxyaniline (VIII) (prepared as described in Preparation 13). The mixture was then stirred at 140°-150° C. for 3 hours, after which 20 ml of diphenyl ether were added, and the mixture was stirred at 240°-250° C. for 1 hour. At the end of this time, the mixture was allowed to cool to room temperature, and then hexane was added to precipitate crystals, which were collected by filtration. 1.60 g of ethyl 6,7-difluoro-4-hydroxy-8-methoxyquinoline-3-carboxylate (IX) were obtained as colorless crystals. the mixture was stirred at 240°-250° C. for 1 hour to precipitate crystals, which were collected by filtration

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

実験手順: 22.6 g (0.422 mole) of ammonium chloride and 38.2 g of reduced iron were added to a solution of 23.0 g (0.114 mole) of 3,4-difluoro-2-methoxy-1-nitrobenzene (VII) [prepared as described in step (a) above] in 1 liter of 80% aqueous methanol. The mixture was then heated under reflux for 4 hours, whilst stirring. At the end of this time, the reaction mixture was filtered, and the filtrate was concentrated by evaporation under reduced pressure. The residue was extracted with toluene. The toluene extract was washed with water, dried, and concentrated by evaporation under reduced pressure to give 10.2 g of 3,4-difluoro-2-methoxyaniline (VIII) as a reddish-brown oil [Step (B2)]. The mixture was then heated under reflux for 4 hours At the end of this time, the reaction mixture was filtered the filtrate was concentrated by evaporation under reduced pressure The residue was extracted with toluene The toluene extract was washed with water dried concentrated by evaporation under reduced pressure

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

実験手順: Into a 200-ml four-necked flask provided with a reflux condenser, a thermometer and a stirrer were fed 7.96 g (0.05 mol) of 3,4-difluoro-2-methoxyaniline, 40 g (0.67 mol) of acetic acid and 100 ml of ethanol. To the resulting mixture being stirred at room temperature was dropwise added 9.24 g (0.053 mol) of 1-ethoxy-1-trimethylsilyloxycyclopropane. The resulting mixture was placed on an oil bath and refluxed at 80° C. for 3 hours with stirring, in a nitrogen current. The resulting reaction mixture was concentrated under aspirator vacuum by the use of a rotary evaporator. Lastly, the acetic acid remaining in the resulting residue was removed by the use of a vacuum pump to obtain 11.5 g of an oily substance. This oily substance was subjected to vacuum distillation to obtain 10.1 g (yield: 83.0%) of N-(1-ethoxy)cyclopropyl-3,4-difluoro-2-methoxyaniline. Into a 200-ml four-necked flask provided with a reflux condenser The resulting mixture was placed on an oil bath refluxed at 80° C. for 3 hours with stirring, in a nitrogen current The resulting reaction mixture was concentrated under aspirator vacuum by the use of a rotary evaporator Lastly, the acetic acid remaining in the resulting residue was removed by the use of a vacuum pump to obtain 11.5 g of an oily substance This oily substance was subjected to vacuum distillation

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

実験手順: 2.84 g (0.013 mole) of diethyl ethoxymethylenemalonate were added to 1.74 g (0.011 mole) of 3,4-difluoro-2-methoxyaniline (VIII) (prepared as described in Preparation 13). The mixture was then stirred at 140°-150° C. for 3 hours, after which 20 ml of diphenyl ether were added, and the mixture was stirred at 240°-250° C. for 1 hour. At the end of this time, the mixture was allowed to cool to room temperature, and then hexane was added to precipitate crystals, which were collected by filtration. 1.60 g of ethyl 6,7-difluoro-4-hydroxy-8-methoxyquinoline-3-carboxylate (IX) were obtained as colorless crystals. the mixture was stirred at 240°-250° C. for 1 hour to precipitate crystals, which were collected by filtration

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

実験手順: 22.6 g (0.422 mole) of ammonium chloride and 38.2 g of reduced iron were added to a solution of 23.0 g (0.114 mole) of 3,4-difluoro-2-methoxy-1-nitrobenzene (VII) [prepared as described in step (a) above] in 1 liter of 80% aqueous methanol. The mixture was then heated under reflux for 4 hours, whilst stirring. At the end of this time, the reaction mixture was filtered, and the filtrate was concentrated by evaporation under reduced pressure. The residue was extracted with toluene. The toluene extract was washed with water, dried, and concentrated by evaporation under reduced pressure to give 10.2 g of 3,4-difluoro-2-methoxyaniline (VIII) as a reddish-brown oil [Step (B2)]. The mixture was then heated under reflux for 4 hours At the end of this time, the reaction mixture was filtered the filtrate was concentrated by evaporation under reduced pressure The residue was extracted with toluene The toluene extract was washed with water dried concentrated by evaporation under reduced pressure