N-benzyl-2,6-difluoro-3,5-dimethoxyaniline

反応条件: temp:-10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: N-Benzyl-2,6-difluoro-3,5-dimethoxyaniline (6.0 g, 21.5 mmol) was dissolved in THF (40 mL) and the solution hydrogenated over 20% palladium hydroxide on carbon catalyst (0.6 g) at 20° C.–25° C. 48–50 psi hydrogen pressure for 16 hours. The mixture was filtered, the catalyst washed with THF (2×15 mL) and the combined filtrates concentrated to a solid. This was recrystallized from heptane (10 mL) and toluene (4.5 mL). The mixture was cooled to −10° C. before filtering. The crystals were washed with heptane (2×10 ML) and vacuum dried at 35° C. to give 2,6-difluoro-3,5-dimethoxyaniline as off-white needles (3.85 g, 20.4 mmol). mp: 78° C.–79° C. The mixture was filtered the catalyst washed with THF (2×15 mL) the combined filtrates concentrated to a solid This was recrystallized from heptane (10 mL) and toluene (4.5 mL) before filtering The crystals were washed with heptane (2×10 ML) and vacuum dried at 35° C.

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

実験手順: 4-(Benzylamino)-3,5-difluoro-2,6-dimethoxybenzoic acid (9.1 g, 28.1 mmol) was treated with chlorobenzene (45 mL) and the solution heated to reflux under nitrogen where it was maintained for 16 hours. The solution was cooled to room temperature and extracted with saturated, aqueous sodium bicarbonate solution (2×5 mL) followed by water. The organic layer was concentrated under reduced pressure to an oil that crystallized on standing. This was recrystallized from heptane (10 mL) and toluene (5 mL), the mixture cooled to −10° C., filtered and the crystals washed with heptane (10 mL) and vacuum dried at 35° C. to give N-benzyl-2,6-difluoro-3,5-dimethoxyaniline (7.4 g, 26.5 mmol). mp: 65° C.–66° C. the solution heated to reflux under nitrogen where it was maintained for 16 hours extracted with saturated, aqueous sodium bicarbonate solution (2×5 mL) The organic layer was concentrated under reduced pressure to an oil that crystallized This was recrystallized from heptane (10 mL) and toluene (5 mL) the mixture cooled to −10° C. filtered the crystals washed with heptane (10 mL) and vacuum dried at 35° C.

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

実験手順: 4-(Benzylamino)-3,5-difluoro-2,6-dimethoxybenzoic acid (9.1 g, 28.1 mmol) was treated with chlorobenzene (45 mL) and the solution heated to reflux under nitrogen where it was maintained for 16 hours. The solution was cooled to room temperature and extracted with saturated, aqueous sodium bicarbonate solution (2×5 mL) followed by water. The organic layer was concentrated under reduced pressure to an oil that crystallized on standing. This was recrystallized from heptane (10 mL) and toluene (5 mL), the mixture cooled to −10° C., filtered and the crystals washed with heptane (10 mL) and vacuum dried at 35° C. to give N-benzyl-2,6-difluoro-3,5-dimethoxyaniline (7.4 g, 26.5 mmol). mp: 65° C.–66° C. the solution heated to reflux under nitrogen where it was maintained for 16 hours extracted with saturated, aqueous sodium bicarbonate solution (2×5 mL) The organic layer was concentrated under reduced pressure to an oil that crystallized This was recrystallized from heptane (10 mL) and toluene (5 mL) the mixture cooled to −10° C. filtered the crystals washed with heptane (10 mL) and vacuum dried at 35° C.

反応条件: temp:-10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: N-Benzyl-2,6-difluoro-3,5-dimethoxyaniline (6.0 g, 21.5 mmol) was dissolved in THF (40 mL) and the solution hydrogenated over 20% palladium hydroxide on carbon catalyst (0.6 g) at 20° C.–25° C. 48–50 psi hydrogen pressure for 16 hours. The mixture was filtered, the catalyst washed with THF (2×15 mL) and the combined filtrates concentrated to a solid. This was recrystallized from heptane (10 mL) and toluene (4.5 mL). The mixture was cooled to −10° C. before filtering. The crystals were washed with heptane (2×10 ML) and vacuum dried at 35° C. to give 2,6-difluoro-3,5-dimethoxyaniline as off-white needles (3.85 g, 20.4 mmol). mp: 78° C.–79° C. The mixture was filtered the catalyst washed with THF (2×15 mL) the combined filtrates concentrated to a solid This was recrystallized from heptane (10 mL) and toluene (4.5 mL) before filtering The crystals were washed with heptane (2×10 ML) and vacuum dried at 35° C.

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

実験手順: 4-(Benzylamino)-3,5-difluoro-2,6-dimethoxybenzoic acid (9.1 g, 28.1 mmol) was treated with chlorobenzene (45 mL) and the solution heated to reflux under nitrogen where it was maintained for 16 hours. The solution was cooled to room temperature and extracted with saturated, aqueous sodium bicarbonate solution (2×5 mL) followed by water. The organic layer was concentrated under reduced pressure to an oil that crystallized on standing. This was recrystallized from heptane (10 mL) and toluene (5 mL), the mixture cooled to −10° C., filtered and the crystals washed with heptane (10 mL) and vacuum dried at 35° C. to give N-benzyl-2,6-difluoro-3,5-dimethoxyaniline (7.4 g, 26.5 mmol). mp: 65° C.–66° C. the solution heated to reflux under nitrogen where it was maintained for 16 hours extracted with saturated, aqueous sodium bicarbonate solution (2×5 mL) The organic layer was concentrated under reduced pressure to an oil that crystallized This was recrystallized from heptane (10 mL) and toluene (5 mL) the mixture cooled to −10° C. filtered the crystals washed with heptane (10 mL) and vacuum dried at 35° C.