phenyl N-(4-fluorophenyl)carbamate

反応条件: temp:85.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: After dissolving N-methyl-4-benzyloxy-2-methylaniline (2.64 g, 11.61 mmol) in N,N-dimethylformamide (20 ml), sodium hydride (1.16 g, 29.00 mmol, 60% in oil) was added and the mixture was stirred at 85° C. for 45 minutes under a nitrogen atmosphere. Phenyl N-(4-fluorophenyl)carbamate (3.50 g, 12.76 mmol) was added and the mixture was further stirred at 85° C. for 1 hour under a nitrogen atmosphere. After cooling to room temperature, water was added to the reaction solution, extraction was performed with ethyl acetate, the extract was washed with saturated saline and dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The residue was adsorbed onto NH silica gel and subjected to crude purification by NH silica gel column chromatography (hexane-ethyl acetate-ethanol) to obtain N′-(4-benzyloxy-2-methylphenyl)-N-(4-fluorophenyl)-N′-methylurea (2.66 g) as a yellow oil. This was dissolved in methanol (50 ml), and then 10% palladium carbon (0.2 g) was added and the mixture was stirred for 2 hours at room temperature under a nitrogen atmosphere. The catalyst was filtered off, the filtrate was washed with ethanol, and the solvent was distilled off under reduced pressure. The precipitated crystals were suspended in ethanol, the suspension was diluted with diethyl ether and hexane, and the crystals were filtered out, washed with hexane and dried by aspiration to obtain the title compound (0.83 g, 3.0258 mmol, 41.86%) as brown crystals. was added the mixture was further stirred at 85° C. for 1 hour under a nitrogen atmosphere After cooling to room temperature the extract was washed with saturated saline dried over anhydrous magnesium sulfate the solvent was distilled off under reduced pressure purification by NH silica gel column chromatography (hexane-ethyl acetate-ethanol)

反応条件: temp:85.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: After dissolving N-methyl-4-benzyloxy-2-methylaniline (2.64 g, 11.61 mmol) in N,N-dimethylformamide (20 ml), sodium hydride (1.16 g, 29.00 mmol, 60% in oil) was added and the mixture was stirred at 85° C. for 45 minutes under a nitrogen atmosphere. Phenyl N-(4-fluorophenyl)carbamate (3.50 g, 12.76 mmol) was added and the mixture was further stirred at 85° C. for 1 hour under a nitrogen atmosphere. After cooling to room temperature, water was added to the reaction solution, extraction was performed with ethyl acetate, the extract was washed with saturated brine and dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The residue was adsorbed onto NH silica gel and subjected to crude purification by NH silica gel column chromatography acetate-ethanol) to obtain N′-(4-benzyloxy-2-methylphenyl)-N-(4-fluorophenyl)-N′-methylurea (2.66 g) as a yellow oil. This was dissolved in methanol (50 ml), and then 10% palladium carbon (0.2 g) was added and the mixture was stirred for 2 hours at room temperature under a hydrogen atmosphere. The catalyst was filtered off, and then filtrate was washed with ethanol, and the solvent was distilled off under reduced pressure. The precipitated crystals were suspended in ethanol, the suspension was diluted with diethyl ether and hexane, and the crystals were filtered out, washed with hexane and dried by aspiration to obtain the title compound (0.83 g, 3.0258 mmol, 41.86%) as brown crystals. was added the mixture was further stirred at 85° C. for 1 hour under a nitrogen atmosphere After cooling to room temperature the extract was washed with saturated brine dried over anhydrous magnesium sulfate the solvent was distilled off under reduced pressure purification by NH silica gel column chromatography acetate-ethanol)

反応条件: temp:85.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: After dissolving N-methyl-4-benzyloxy-2-methylaniline (2.64 g, 11.61 mmol) in N,N-dimethylformamide (20 ml), sodium hydride (1.16 g, 29.00 mmol, 60% in oil) was added and the mixture was stirred at 85° C. for 45 minutes under a nitrogen atmosphere. Phenyl N-(4-fluorophenyl)carbamate (3.50 g, 12.76 mmol) was added and the mixture was further stirred at 85° C. for 1 hour under a nitrogen atmosphere. After cooling to room temperature, water was added to the reaction solution, extraction was performed with ethyl acetate, the extract was washed with saturated brine and dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The residue was adsorbed onto NH silica gel and subjected to crude purification by NH silica gel column chromatography (hexane-ethyl acetate-ethanol) to obtain N′-(4-benzyloxy-2-methylphenyl)-N-(4-fluorophenyl)-N′-methylurea (2.66 g) as a yellow oil. This was dissolved in methanol (50 ml), and then 10% palladium carbon (0.2 g) was added and the mixture was stirred for 2 hours at room temperature under a hydrogen atmosphere. The catalyst was filtered off, and then filtrate was washed with ethanol, and the solvent was distilled off under reduced pressure. The precipitated crystals were suspended in ethanol, the suspension was diluted with diethyl ether and hexane, and the crystals were filtered out, washed with hexane and dried by aspiration to obtain the title compound (0.83 g, 3.0258 mmol, 41.86%) as brown crystals. was added the mixture was further stirred at 85° C. for 1 hour under a nitrogen atmosphere After cooling to room temperature the extract was washed with saturated brine dried over anhydrous magnesium sulfate the solvent was distilled off under reduced pressure purification by NH silica gel column chromatography (hexane-ethyl acetate-ethanol)

反応条件: temp:85.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: After dissolving N-methyl-4-benzyloxy-2-methylaniline (2.64 g, 11.61 mmol) in N,N-dimethylformamide (20 ml), sodium hydride (1.16 g, 29.00 mmol, 60% in oil) was added and the mixture was stirred at 85° C. for 45 minutes under a nitrogen atmosphere. Phenyl N-(4-fluorophenyl)carbamate (3.50 g, 12.76 mmol) was added and the mixture was further stirred at 85° C. for 1 hour under a nitrogen atmosphere. After cooling to room temperature, water was added to the reaction solution, extraction was performed with ethyl acetate, the extract was washed with saturated saline and dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The residue was adsorbed onto NH silica gel and subjected to crude purification by NH silica gel column chromatography (hexane-ethyl acetate-ethanol) to obtain N′-(4-benzyloxy-2-methylphenyl)-N-(4-fluorophenyl)-N′-methylurea (2.66 g) as a yellow oil. This was dissolved in methanol (50 ml), and then 10% palladium carbon (0.2 g) was added and the mixture was stirred for 2 hours at room temperature under a nitrogen atmosphere. The catalyst was filtered off, the filtrate was washed with ethanol, and the solvent was distilled off under reduced pressure. The precipitated crystals were suspended in ethanol, the suspension was diluted with diethyl ether and hexane, and the crystals were filtered out, washed with hexane and dried by aspiration to obtain the title compound (0.83 g, 3.0258 mmol, 41.86%) as brown crystals. was added the mixture was further stirred at 85° C. for 1 hour under a nitrogen atmosphere After cooling to room temperature the extract was washed with saturated saline dried over anhydrous magnesium sulfate the solvent was distilled off under reduced pressure purification by NH silica gel column chromatography (hexane-ethyl acetate-ethanol)

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

実験手順: A solution of 4-fluoro-N-phenoxycarbonylaniline (2.29 g), N-amino-1,2,3,6-tetrahydropyridine hydrochloride (1.346 g) and triethylamine (1.02 g) in chloroform (25 ml) was refluxed for 20 hours. After evaporation of chloroform, the residue was extracted with ethyl acetate (100 ml). The extract was washed with water, dried over magnesium sulfate and evaporated in vacuo. The residue was chromatographed on silica gel (20 g) using chloroform as an eluent to give N-[[(4-fluorophenyl)carbamoyl]amino]-1,2,3,6-tetrahydropyridine (1.05 g). mp: 156°-157° C. After evaporation of chloroform the residue was extracted with ethyl acetate (100 ml) The extract was washed with water dried over magnesium sulfate evaporated in vacuo The residue was chromatographed on silica gel (20 g)

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

実験手順: A solution of 4-fluoro-N-phenoxycarbonylaniline (2.29 g), N-amino-1,2,3,6-tetrahydropyridine hydrochloride (1.346 g) and triethylamine (1.02 g) in chloroform (25 ml) was refluxed for 20 hours. After evaporation of chloroform, the residue was extracted with ethyl acetate (100 ml). The extract was washed with water, dried over magnesium sulfate and evaporated in vacuo. The residue was chromatographed on silica gel (20 g) using chloroform as an eluent to give N-[[(4-fluorophenyl)carbamoyl]amino]-1,2,3,6-tetrahydropyridine (1.05 g). mp: 156°-157° C. After evaporation of chloroform the residue was extracted with ethyl acetate (100 ml) The extract was washed with water dried over magnesium sulfate evaporated in vacuo The residue was chromatographed on silica gel (20 g)

反応条件: temp:85.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: After dissolving N-methyl-4-benzyloxy-2-methylaniline (2.64 g, 11.61 mmol) in N,N-dimethylformamide (20 ml), sodium hydride (1.16 g, 29.00 mmol, 60% in oil) was added and the mixture was stirred at 85° C. for 45 minutes under a nitrogen atmosphere. Phenyl N-(4-fluorophenyl)carbamate (3.50 g, 12.76 mmol) was added and the mixture was further stirred at 85° C. for 1 hour under a nitrogen atmosphere. After cooling to room temperature, water was added to the reaction solution, extraction was performed with ethyl acetate, the extract was washed with saturated brine and dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The residue was adsorbed onto NH silica gel and subjected to crude purification by NH silica gel column chromatography (hexane-ethyl acetate-ethanol) to obtain N′-(4-benzyloxy-2-methylphenyl)-N-(4-fluorophenyl)-N′-m ethylurea (2.66 g) as a yellow oil. This was dissolved in methanol (50 ml), and then 10% palladium carbon (0.2 g) was added and the mixture was stirred for 2 hours at room temperature under a hydrogen atmosphere. The catalyst was filtered off, and then filtrate was washed with ethanol, and the solvent was distilled off under reduced pressure. The precipitated crystals were suspended in ethanol, the suspension was diluted with diethyl ether and hexane, and the crystals were filtered out, washed with hexane and dried by aspiration to obtain the title compound (0.83 g, 3.0258 mmol, 41.86%) as brown crystals. was added the mixture was further stirred at 85° C. for 1 hour under a nitrogen atmosphere After cooling to room temperature the extract was washed with saturated brine dried over anhydrous magnesium sulfate the solvent was distilled off under reduced pressure purification by NH silica gel column chromatography (hexane-ethyl acetate-ethanol)

反応条件: temp:85.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: After dissolving N-methyl-4-benzyloxy-2-methylaniline (2.64 g, 11.61 mmol) in N,N-dimethylformamide (20 ml), sodium hydride (1.16 g, 29.00 mmol, 60% in oil) was added and the mixture was stirred at 85° C. for 45 minutes under a nitrogen atmosphere. Phenyl N-(4-fluorophenyl)carbamate (3.50 g, 12.76 mmol) was added and the mixture was further stirred at 85° C. for 1 hour under a nitrogen atmosphere. After cooling to room temperature, water was added to the reaction solution, extraction was performed with ethyl acetate, the extract was washed with saturated brine and dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The residue was adsorbed onto NH silica gel and subjected to crude purification by NH silica gel column chromatography acetate-ethanol) to obtain N′-(4-benzyloxy-2-methylphenyl)-N-(4-fluorophenyl)-N′-methylurea (2.66 g) as a yellow oil. This was dissolved in methanol (50 ml), and then 10% palladium carbon (0.2 g) was added and the mixture was stirred for 2 hours at room temperature under a hydrogen atmosphere. The catalyst was filtered off, and then filtrate was washed with ethanol, and the solvent was distilled off under reduced pressure. The precipitated crystals were suspended in ethanol, the suspension was diluted with diethyl ether and hexane, and the crystals were filtered out, washed with hexane and dried by aspiration to obtain the title compound (0.83 g, 3.0258 mmol, 41.86%) as brown crystals. was added the mixture was further stirred at 85° C. for 1 hour under a nitrogen atmosphere After cooling to room temperature the extract was washed with saturated brine dried over anhydrous magnesium sulfate the solvent was distilled off under reduced pressure purification by NH silica gel column chromatography acetate-ethanol)

反応条件: temp:85.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: After dissolving N-methyl-4-benzyloxy-2-methylaniline (2.64 g, 11.61 mmol) in N,N-dimethylformamide (20 ml), sodium hydride (1.16 g, 29.00 mmol, 60% in oil) was added and the mixture was stirred at 85° C. for 45 minutes under a nitrogen atmosphere. Phenyl N-(4-fluorophenyl)carbamate (3.50 g, 12.76 mmol) was added and the mixture was further stirred at 85° C. for 1 hour under a nitrogen atmosphere. After cooling to room temperature, water was added to the reaction solution, extraction was performed with ethyl acetate, the extract was washed with saturated brine and dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The residue was adsorbed onto NH silica gel and subjected to crude purification by NH silica gel column chromatography (hexane-ethyl acetate-ethanol) to obtain N′-(4-benzyloxy-2-methylphenyl)-N-(4-fluorophenyl)-N′-methylurea (2.66 g) as a yellow oil. This was dissolved in methanol (50 ml), and then 10% palladium carbon (0.2 g) was added and the mixture was stirred for 2 hours at room temperature under a hydrogen atmosphere. The catalyst was filtered off, and then filtrate was washed with ethanol, and the solvent was distilled off under reduced pressure. The precipitated crystals were suspended in ethanol, the suspension was diluted with diethyl ether and hexane, and the crystals were filtered out, washed with hexane and dried by aspiration to obtain the title compound (0.83 g, 3.0258 mmol, 41.86%) as brown crystals. was added the mixture was further stirred at 85° C. for 1 hour under a nitrogen atmosphere After cooling to room temperature the extract was washed with saturated brine dried over anhydrous magnesium sulfate the solvent was distilled off under reduced pressure purification by NH silica gel column chromatography (hexane-ethyl acetate-ethanol)

反応条件: temp:85.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: After dissolving N-methyl-4-benzyloxy-2-methylaniline (2.64 g, 11.61 mmol) in N,N-dimethylformamide (20 ml), sodium hydride (1.16 g, 29.00 mmol, 60% in oil) was added and the mixture was stirred at 85° C. for 45 minutes under a nitrogen atmosphere. Phenyl N-(4-fluorophenyl)carbamate (3.50 g, 12.76 mmol) was added and the mixture was further stirred at 85° C. for 1 hour under a nitrogen atmosphere. After cooling to room temperature, water was added to the reaction solution, extraction was performed with ethyl acetate, the extract was washed with saturated saline and dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The residue was adsorbed onto NH silica gel and subjected to crude purification by NH silica gel column chromatography (hexane-ethyl acetate-ethanol) to obtain N′-(4-benzyloxy-2-methylphenyl)-N-(4-fluorophenyl)-N′-methylurea (2.66 g) as a yellow oil. This was dissolved in methanol (50 ml), and then 10% palladium carbon (0.2 g) was added and the mixture was stirred for 2 hours at room temperature under a nitrogen atmosphere. The catalyst was filtered off, the filtrate was washed with ethanol, and the solvent was distilled off under reduced pressure. The precipitated crystals were suspended in ethanol, the suspension was diluted with diethyl ether and hexane, and the crystals were filtered out, washed with hexane and dried by aspiration to obtain the title compound (0.83 g, 3.0258 mmol, 41.86%) as brown crystals. was added the mixture was further stirred at 85° C. for 1 hour under a nitrogen atmosphere After cooling to room temperature the extract was washed with saturated saline dried over anhydrous magnesium sulfate the solvent was distilled off under reduced pressure purification by NH silica gel column chromatography (hexane-ethyl acetate-ethanol)

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

実験手順: A solution of 4-fluoro-N-phenoxycarbonylaniline (2.29 g), N-amino-1,2,3,6-tetrahydropyridine hydrochloride (1.346 g) and triethylamine (1.02 g) in chloroform (25 ml) was refluxed for 20 hours. After evaporation of chloroform, the residue was extracted with ethyl acetate (100 ml). The extract was washed with water, dried over magnesium sulfate and evaporated in vacuo. The residue was chromatographed on silica gel (20 g) using chloroform as an eluent to give N-[[(4-fluorophenyl)carbamoyl]amino]-1,2,3,6-tetrahydropyridine (1.05 g). mp: 156°-157° C. After evaporation of chloroform the residue was extracted with ethyl acetate (100 ml) The extract was washed with water dried over magnesium sulfate evaporated in vacuo The residue was chromatographed on silica gel (20 g)