N,N-dimethyloxan-4-amine

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: To a solution of N-(4-chloromethylphenyl)-7-(4-ethoxyphenyl)-2,3-dihydro-1-benzoxepine-4-carboxamide (2.38 g) in DMF (20 ml) was added N,N-dimethyl-N-tetrahydropyran-4-ylamine (1.42 g) at room temperature, and the mixture was stirred for 14 hours. To the reaction mixture was added ethyl acetate (100 ml) to precipitate crystals, which were collected by filtration. The crystal was washed with ethyl acetate to give crude product as pale yellow crystals, which were recrystallized from ethanol to give as N-(4-(((7-(4-ethoxyphenyl)-2,3-dihydro-1-benzoxepin-4-yl)carbonyl)amino)benzyl)-N,N-dimethyl-N-(4-tetrahydropyranyl)ammonium chloride (Compound 3) (1.29 g) colorless crystals. to precipitate crystals, which were collected by filtration The crystal was washed with ethyl acetate to give crude product as pale yellow crystals, which were recrystallized from ethanol

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

実験手順: To a solution of N-(4-chloromethylphenyl)-7-(4-ethoxyphenyl)-2,3-dihydro-1-benzoxepine-4-carboxamide (2.38 g) in DMF (20 ml) was added N,N-dimethyl-N-tetrahydropyran-4-ylamine (1.42 g) at room temperature, and the mixture was stirred for 14 hours. To the reaction mixture was added ethyl acetate (100 ml) to precipitate crystals, which were collected by filtration. The crystal was washed with ethyl acetate to give crude product as pale yellow crystals, which were recrystallized from ethanol to give as N-(4-(((7-(4-ethoxyphenyl)-2,3-dihydro-1-benzoxepin-4-yl)carbonyl)amino)benzyl)-N,N-dimethyl-N-(4-tetrahydropyranyl)ammonium chloride (Compound 3) (1.29 g) colorless crystals. to precipitate crystals, which were collected by filtration The crystal was washed with ethyl acetate to give crude product as pale yellow crystals, which were recrystallized from ethanol

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

実験手順: To a solution of N-(4-chloromethylphenyl)-2-(4-methylphenyl)-6,7-dihydro-5H-benzocycloheptene-8-carboxamide (9.38 g, 23.3 mmol) in DMF (50 ml) was dropwise added a solution of N,N-dimethyl-N-tetrahydropyran-4-ylamine (4.5 g, 35.0 mmol) in DMF (50 ml). Under nitrogen atmosphere, the mixture was stirred for 23 hours. The solvent was evaporated to give powder, which was washed with acetone and dried. The resulting colorless powder was recrystallized from ethanol to give N,N-dimethyl-N-(4-(((2-(4-methylphenyl)-6,7-dihydro-5H-benzocyclohepten-8-yl)carbonyl)amino)benzyl)-N-(4-tetrahydropyranyl)ammonium chloride (Compound 1) (10.6 g, 86%) as colorless powder. The solvent was evaporated to give powder, which was washed with acetone dried The resulting colorless powder was recrystallized from ethanol

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

実験手順: To a solution of N-(4-chloromethylphenyl)-7-(4-ethoxyphenyl)-2,3-dihydro-1-benzoxepine-4-carboxamide (2.38 g) in DMF (20 ml) was added N,N-dimethyl-N-tetrahydropyran-4-ylamine (1.42 g) at room temperature, and the mixture was stirred for 14 hours. To the reaction mixture was added ethyl acetate (100 ml) to precipitate crystals, which were collected by filtration. The crystal was washed with ethyl acetate to give crude product as pale yellow crystals, which were recrystallized from ethanol to give as N-(4-(((7-(4-ethoxyphenyl)-2,3-dihydro-1-benzoxepin-4-yl)carbonyl)amino)benzyl)-N,N-dimethyl-N-(4-tetrahydropyranyl)ammonium chloride (Compound 250) (1.29 g) colorless crystals. to precipitate crystals, which were collected by filtration The crystal was washed with ethyl acetate to give crude product as pale yellow crystals, which were recrystallized from ethanol

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

実験手順: To a solution of N-(4-chloromethylphenyl)-2-(4-methylphenyl)-6,7-dihydro-5H-benzocycloheptene-8-carboxamide (9.38 g, 23.3 mmol) in DMF (50 ml) was dropwise added a solution of N,N-dimethyl-N-tetrahydropyran-4-ylamine (4.5 g, 35.0 mmol) in DMF (50 ml). Under nitrogen atmosphere, the mixture was stirred for 23 hours. The solvent was evaporated to give powder, which was washed with acetone and dried. The resulting colorless powder was recrystallized from ethanol to give N,N-dimethyl-N-(4-(((2-(4-methylphenyl)-6,7-dihydro-5H-benzocyclohepten-8-yl)carbonyl)amino)benzyl)-N-(4-tetrahydropyranyl)ammonium chloride (Compound 248) (10.6 g, 86%) as colorless powder. The solvent was evaporated to give powder, which was washed with acetone dried The resulting colorless powder was recrystallized from ethanol

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

実験手順: Into a reaction device similar to that used in Example 9 were charged 50.0 g (0.5 mol) of tetrahydropyran-4-one, 180.0 g (2.0 mol) of 50% by weight aqueous dimethylamine solution and 20 g (9 mmol in terms of a palladium atom) of 5% by weight Pd/C, and the mixture was reacted at a hydrogen pressure of 0.2 to 0.4 MPa at 50° C. for 7 hours and further at 70° C. for 4 hours. After completion of the reaction, the resulting reaction mixture was cooled to room temperature and the catalyst was filtered off by Celite, and the filtrate was made acidic (pH=1) by adding 60 ml of conc. sulfuric acid and then washed successively with 200 ml of 2-butanol twice and 200 ml of chloroform twice. Then, 130 g of potassium hydroxide was added to the aqueous layer to make the solution basic (pH=11), the aqueous layer was extracted three times with each 300 ml of ethyl acetate and the resulting organic layer was dried over anhydrous magnesium sulfate. After filtration, the organic layer was concentrated under reduced pressure, and then, by distillation under reduced pressure (83 to 85° C., 50 mmHg), 12.4 g (yield: 19%) of 4-dimethylaminotetrahydropyrane with a purity of 99% (areal percentage according to gas chromatography) as a colorless liquid. After completion of the reaction the resulting reaction mixture the catalyst was filtered off by Celite by adding 60 ml of conc. sulfuric acid washed successively with 200 ml of 2-butanol twice Then, 130 g of potassium hydroxide was added to the aqueous layer the aqueous layer was extracted three times with each 300 ml of ethyl acetate the resulting organic layer was dried over anhydrous magnesium sulfate After filtration the organic layer was concentrated 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 reaction device similar to that used in Example 9 were charged 50.0 g (0.5 mol) of tetrahydropyran-4-one, 180.0 g (2.0 mol) of 50% by weight aqueous dimethylamine solution and 20 g (9 mmol in terms of a palladium atom) of 5% by weight Pd/C, and the mixture was reacted at a hydrogen pressure of 0.2 to 0.4 MPa at 50° C. for 7 hours and further at 70° C. for 4 hours. After completion of the reaction, the resulting reaction mixture was cooled to room temperature and the catalyst was filtered off by Celite, and the filtrate was made acidic (pH=1) by adding 60 ml of conc. sulfuric acid and then washed successively with 200 ml of 2-butanol twice and 200 ml of chloroform twice. Then, 130 g of potassium hydroxide was added to the aqueous layer to make the solution basic (pH=11), the aqueous layer was extracted three times with each 300 ml of ethyl acetate and the resulting organic layer was dried over anhydrous magnesium sulfate. After filtration, the organic layer was concentrated under reduced pressure, and then, by distillation under reduced pressure (83 to 85° C., 50 mmHg), 12.4 g (yield: 19%) of 4-dimethylaminotetrahydropyrane with a purity of 99% (areal percentage according to gas chromatography) as a colorless liquid. After completion of the reaction the resulting reaction mixture the catalyst was filtered off by Celite by adding 60 ml of conc. sulfuric acid washed successively with 200 ml of 2-butanol twice Then, 130 g of potassium hydroxide was added to the aqueous layer the aqueous layer was extracted three times with each 300 ml of ethyl acetate the resulting organic layer was dried over anhydrous magnesium sulfate After filtration the organic layer was concentrated under reduced pressure

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: To a solution of N-(4-chloromethylphenyl)-2-(4-methylphenyl)-6,7-dihydro-5H-benzocycloheptene-8-carboxamide (9.38 g, 23.3 mmol) in DMF (50 ml) was dropwise added a solution of N,N-dimethyl-N-tetrahydropyran-4-ylamine (4.5 g, 35.0 mmol) in DMF (50 ml). Under nitrogen atmosphere, the mixture was stirred for 23 hours. The solvent was evaporated to give powder, which was washed with acetone and dried. The resulting colorless powder was recrystallized from ethanol to give N,N-dimethyl-N-(4-(((2-(4-methylphenyl)-6,7-dihydro-5H-benzocyclohepten-8-yl)carbonyl)amino)benzyl)-N-(4-tetrahydropyranyl)-ammonium chloride (Compound 248) (10.6 g, 86%) as colorless powder. The solvent was evaporated to give powder, which was washed with acetone dried The resulting colorless powder was recrystallized from ethanol

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

実験手順: To a solution of N-(4-chloromethylphenyl)-2-(4-methylphenyl)-6,7-dihydro-5H-benzocycloheptene-8-carboxamide (9.38 g, 23.3 mmol) in DMF (50 ml) was dropwise added a solution of N,N-dimethyl-N-tetrahydropyran-4-ylamine (4.5 g, 35.0 mmol) in DMF (50 ml). Under nitrogen atmosphere, the mixture was stirred for 23 hours. The solvent was evaporated to give powder, which was washed with acetone and dried. The resulting colorless powder was recrystallized from ethanol to give N,N-dimethyl-N-(4-(((2-(4-methylphenyl)-6,7-dihydro-5H-benzocyclohepten-8-yl)carbonyl)amino)benzyl)-N-(4-tetrahydropyranyl)-ammonium chloride (Compound 248) (10.6 g, 86%) as colorless powder. The solvent was evaporated to give powder, which was washed with acetone dried The resulting colorless powder was recrystallized from ethanol