1-(3-fluoro-4-methylphenyl)-2-methylpropan-2-amine

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2-Chloro-N-[1-(3-fluoro-4-methylphenyl)-2-methylpropan-2-yl]acetamide (131.6 g) obtained in Step 6 was dissolved in acetic acid (200 ml) and ethanol (1 L), and thiourea (46.6 g) was added. The mixture was stirred overnight at 100° C. The reaction mixture was cooled to room temperature, and the precipitated crystals were filtered. The filtrate was concentrated under reduced pressure, and 4N-sodium hydroxide solution (300 ml) was added to the obtained residue. The mixture was extracted 3 times with toluene. The organic layer was washed with brine, and concentrated under reduced pressure. The obtained residue was dissolved in diethyl ether (1 L) and 4N-hydrochloric acid/ethyl acetate solution (255 ml) was added dropwise under ice-cooling. The mixture was stirred for 1 hr and the precipitated crystals were collected by filtration. The obtained crystals were added to a mixture of toluene and 4N-aqueous sodium hydroxide solution. The toluene layer was separated, washed twice with water, and concentrated under reduced pressure to give the title compound (57.9 g). The reaction mixture was cooled to room temperature the precipitated crystals were filtered The filtrate was concentrated under reduced pressure, and 4N-sodium hydroxide solution (300 ml) was added to the obtained residue The mixture was extracted 3 times with toluene The organic layer was washed with brine concentrated under reduced pressure The obtained residue was dissolved in diethyl ether (1 L) 4N-hydrochloric acid/ethyl acetate solution (255 ml) was added dropwise under ice- cooling The mixture was stirred for 1 hr the precipitated crystals were collected by filtration The obtained crystals were added to a mixture of toluene and 4N-aqueous sodium hydroxide solution The toluene layer was separated washed twice with water concentrated under reduced pressure

反応条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2-Chloro-N-[1-(3-fluoro-4-methylphenyl)-2-methylpropan-2-yl]acetamide (131.6 g) obtained in Step 6 was dissolved in acetic acid (200 ml) and ethanol (1 L), and thiourea (46.6 g) was added. The mixture was stirred overnight at 100° C. The reaction mixture was cooled to room temperature, and the precipitated crystals were filtered. The filtrate was concentrated under reduced pressure, and 4N-sodium hydroxide solution (300 ml) was added to the obtained residue. The mixture was extracted 3 times with toluene. The organic layer was washed with brine, and concentrated under reduced pressure. The obtained residue was dissolved in diethyl ether (1 L) and 4N-hydrochloric acid/ethyl acetate solution (255 ml) was added dropwise under ice-cooling. The mixture was stirred for 1 hr and the precipitated crystals were collected by filtration. The obtained crystals were added to a mixture of toluene and 4N-aqueous sodium hydroxide solution. The toluene layer was separated, washed twice with water, and concentrated under reduced pressure to give the title compound (57.9 g). The reaction mixture was cooled to room temperature the precipitated crystals were filtered The filtrate was concentrated under reduced pressure, and 4N-sodium hydroxide solution (300 ml) was added to the obtained residue The mixture was extracted 3 times with toluene The organic layer was washed with brine concentrated under reduced pressure The obtained residue was dissolved in diethyl ether (1 L) 4N-hydrochloric acid/ethyl acetate solution (255 ml) was added dropwise under ice- cooling The mixture was stirred for 1 hr the precipitated crystals were collected by filtration The obtained crystals were added to a mixture of toluene and 4N-aqueous sodium hydroxide solution The toluene layer was separated washed twice with water concentrated under reduced pressure

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2-Chloro-N-[1-(3-fluoro-4-methylphenyl)-2-methylpropan-2-yl]acetamide (131.6 g) obtained in Step 6 was dissolved in acetic acid (200 ml) and ethanol (1 L), and thiourea (46.6 g) was added. The mixture was stirred overnight at 100° C. The reaction mixture was cooled to room temperature, and the precipitated crystals were filtered. The filtrate was concentrated under reduced pressure, and 4N-sodium hydroxide solution (300 ml) was added to the obtained residue. The mixture was extracted 3 times with toluene. The organic layer was washed with brine, and concentrated under reduced pressure. The obtained residue was dissolved in diethyl ether (1 L) and 4N-hydrochloric acid/ethyl acetate solution (255 ml) was added dropwise under ice-cooling. The mixture was stirred for 1 hr and the precipitated crystals were collected by filtration. The obtained crystals were added to a mixture of toluene and 4N-aqueous sodium hydroxide solution. The toluene layer was separated, washed twice with water, and concentrated under reduced pressure to give the title compound (57.9 g). The reaction mixture was cooled to room temperature the precipitated crystals were filtered The filtrate was concentrated under reduced pressure, and 4N-sodium hydroxide solution (300 ml) was added to the obtained residue The mixture was extracted 3 times with toluene The organic layer was washed with brine concentrated under reduced pressure The obtained residue was dissolved in diethyl ether (1 L) 4N-hydrochloric acid/ethyl acetate solution (255 ml) was added dropwise under ice- cooling The mixture was stirred for 1 hr the precipitated crystals were collected by filtration The obtained crystals were added to a mixture of toluene and 4N-aqueous sodium hydroxide solution The toluene layer was separated washed twice with water concentrated under reduced pressure

反応条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2-Chloro-N-[1-(3-fluoro-4-methylphenyl)-2-methylpropan-2-yl]acetamide (131.6 g) obtained in Step 6 was dissolved in acetic acid (200 ml) and ethanol (1 L), and thiourea (46.6 g) was added. The mixture was stirred overnight at 100° C. The reaction mixture was cooled to room temperature, and the precipitated crystals were filtered. The filtrate was concentrated under reduced pressure, and 4N-sodium hydroxide solution (300 ml) was added to the obtained residue. The mixture was extracted 3 times with toluene. The organic layer was washed with brine, and concentrated under reduced pressure. The obtained residue was dissolved in diethyl ether (1 L) and 4N-hydrochloric acid/ethyl acetate solution (255 ml) was added dropwise under ice-cooling. The mixture was stirred for 1 hr and the precipitated crystals were collected by filtration. The obtained crystals were added to a mixture of toluene and 4N-aqueous sodium hydroxide solution. The toluene layer was separated, washed twice with water, and concentrated under reduced pressure to give the title compound (57.9 g). The reaction mixture was cooled to room temperature the precipitated crystals were filtered The filtrate was concentrated under reduced pressure, and 4N-sodium hydroxide solution (300 ml) was added to the obtained residue The mixture was extracted 3 times with toluene The organic layer was washed with brine concentrated under reduced pressure The obtained residue was dissolved in diethyl ether (1 L) 4N-hydrochloric acid/ethyl acetate solution (255 ml) was added dropwise under ice- cooling The mixture was stirred for 1 hr the precipitated crystals were collected by filtration The obtained crystals were added to a mixture of toluene and 4N-aqueous sodium hydroxide solution The toluene layer was separated washed twice with water concentrated under reduced pressure