2-(difluoromethoxy)aniline

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

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-difluoromethoxyaniline (7.63 g) and the product from step a) were stirred in acetonitrile (100 ml) overnight. The solvent was removed by evaporation and the solid triturated with 4:1 isohexane/diethyl ether (200 ml) before filtering to give a light green solid. The solid was added portionwise to refluxing diphenylether (120 ml) and continued heating for a further 10 minutes before cooling. The solution was poured into isohexane (600 ml) and the solid filtered off to give the title compound (12.0 g). The solvent was removed by evaporation the solid triturated with 4:1 isohexane/diethyl ether (200 ml) before filtering to give a light green solid The solid was added portionwise continued heating for a further 10 minutes before cooling the solid filtered off

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

実験手順: 2-difluoromethoxyaniline (7.63 g) and the product from step a) were stirred in acetonitrile (100 ml) overnight. The solvent was removed by evaporation and the solid triturated with 4:1 isohexane/diethyl ether (200 ml) before filtering to give a light green solid. The solid was added portionwise to refluxing diphenylether (120 ml) and continued heating for a further 10 minutes before cooling. The solution was poured into isohexane (600 ml) and the solid filtered off to give the title compound (12.0 g). The solvent was removed by evaporation the solid triturated with 4:1 isohexane/diethyl ether (200 ml) before filtering to give a light green solid The solid was added portionwise continued heating for a further 10 minutes before cooling the solid filtered off

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

実験手順: 2-difluoromethoxyaniline (7.63 g) and the product from step a) were stirred in acetonitrile (100 ml) overnight. The solvent was removed by evaporation and the solid triturated with 4:1 isohexane/diethyl ether (200 ml) before filtering to give a light green solid. The solid was added portionwise to refluxing diphenylether (120 ml) and continued heating for a further 10 minutes before cooling. The solution was poured into isohexane (600 ml) and the solid filtered off to give the title compound (12.0 g). The solvent was removed by evaporation the solid triturated with 4:1 isohexane/diethyl ether (200 ml) before filtering to give a light green solid The solid was added portionwise continued heating for a further 10 minutes before cooling the solid filtered off

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

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

実験手順: A mixture of 2-difluoromethoxyaniline (5.14 g, 32.3 mmol) and bis(chloroethyl)amine hydrochloride (5.8 g, 32.5 mmol) in 50 mL of n-butanol was heated at reflux for 48 hours. Potassium carbonate (8.9 g, 64.5 mmol) was added and heated at reflux for approximately 24 hours. The mixture was extracted with 2N hydrochloric acid and the extract cooled to approximately 0° C. and then basified with sodium hydroxide to give a precipitate. The precipitate was extracted with ethyl acetate. The ethyl acetate extract was washed with brine, dried (MgSO4) and concentrated. The residue was purified by column chromatography eluting with 5% methanol/methylene chloride. Product fractions were combined and concentrated. The residue was crystallized from hydrochloric acid in methanol to give 1-[2-(difluoromethoxy)phenyl]piperazine hydrochloride (1.32 g, 4.38 mmol), m.p. 165°-176° C. was heated at reflux for 48 hours heated at reflux for approximately 24 hours The mixture was extracted with 2N hydrochloric acid to give a precipitate The precipitate was extracted with ethyl acetate The ethyl acetate extract was washed with brine dried (MgSO4) concentrated The residue was purified by column chromatography eluting with 5% methanol/methylene chloride concentrated The residue was crystallized from hydrochloric acid in methanol

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

実験手順: A mixture of 2-difluoromethoxyaniline (5.14 g, 32.3 mmol) and bis(chloroethyl)amine hydrochloride (5.8 g, 32.5 mmol) in 50 mL of n-butanol was heated at reflux for 48 hours. Potassium carbonate (8.9 g, 64.5 mmol) was added and heated at reflux for approximately 24 hours. The mixture was extracted with 2N hydrochloric acid and the extract cooled to approximately 0° C. and then basified with sodium hydroxide to give a precipitate. The precipitate was extracted with ethyl acetate. The ethyl acetate extract was washed with brine, dried (MgSO4) and concentrated. The residue was purified by column chromatography eluting with 5% methanol/methylene chloride. Product fractions were combined and concentrated. The residue was crystallized from hydrochloric acid in methanol to give 1-[2-(difluoromethoxy)phenyl]piperazine hydrochloride (1.32 g, 4.38 mmol), m.p. 165°-176° C. was heated at reflux for 48 hours heated at reflux for approximately 24 hours The mixture was extracted with 2N hydrochloric acid to give a precipitate The precipitate was extracted with ethyl acetate The ethyl acetate extract was washed with brine dried (MgSO4) concentrated The residue was purified by column chromatography eluting with 5% methanol/methylene chloride concentrated The residue was crystallized from hydrochloric acid in methanol