phenyl N-(2,4-difluorophenyl)carbamate

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: After dissolving 2,4-difluoroaniline (10 ml, 98.21 mmol) in tetrahydrofuran (200 ml), pyridine (8.7 ml, 108.33 mmol) was added at room temperature and the mixture was stirred. It was then cooled on ice, phenyl chloroformate (13.6 ml, 108.33 mmol) was added dropwise over 15 minutes, and the mixture was then stirred at room temperature for 24 hours. Water was added to the reaction solution, extraction was performed with ethyl acetate and tetrahydrofuran, the extract was washed with saturated saline and dried over anhydrous magnesium sulfate, and the filtrate was distilled off under reduced pressure. The obtained crystals were suspended in ethanol and diluted with hexane, and then the crystals were filtered out, washed with hexane and dried by aspiration to obtain the title compound (21.00 g, 84.26 mmol, 85.80%) as light violet crystals. was added at room temperature was added dropwise over 15 minutes the mixture was then stirred at room temperature for 24 hours the extract was washed with saturated saline dried over anhydrous magnesium sulfate the filtrate was distilled off under reduced pressure diluted with hexane the crystals were filtered out washed with hexane dried by aspiration

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

実験手順: After dissolving 6-carbamoyl-4-(1H-indol-5-yloxy)-7-methoxyquinoline (100 mg, 0.3 mmol) in N,N-dimethylformamide (0.5 ml), there was added sodium hydride (12 mg, 0.3 mmol) while cooling on ice and the mixture was stirred at room temperature for 15 minutes. After adding phenyl N-(2,4-difluorophenyl)carbamate (79 mg, 0.3150 mmol), the mixture was stirred at room temperature for 2 hours. Water was added to the reaction solution, extraction was performed with ethyl acetate and tetrahydrofuran, the extract was washed with saturated saline and dried over anhydrous magnesium sulfate, and the filtrate was distilled off under reduced pressure. The obtained crystals were suspended in ethanol and diluted with hexane, and then the crystals were filtered out, washed with hexane and dried by aspiration to obtain the title compound (84 mg, 0.1718 mmol, 57.28%) as colorless crystals. while cooling on ice the mixture was stirred at room temperature for 2 hours the extract was washed with saturated saline dried over anhydrous magnesium sulfate the filtrate was distilled off under reduced pressure diluted with hexane the crystals were filtered out washed with hexane dried by aspiration

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

実験手順: A mixture of 1.58 g of 6-[[(4-butylphenyl)methyl]amino]-1-hexanol and 1.5 g of phenyl-N-(2,4-difluorophenyl)carbamate in 40 ml of toluene was heated at reflux for 5 hours. The reaction mixture was cooled and allowed to stand at room temperature for 16 hours. The solution was washed with 3N aqueous hydrochloric acid, brine, 1N aqueous sodium hydroxide and brine again, then was dried over anhydrous magnesium sulfate and filtered. The filtrate was evaporated in vacuo and gave a yellow oil. The oil was treated by preparative high pressure liquid chromatography and gave 0.93 g (37%) of the desired product as a colorless oil. was heated at reflux for 5 hours The reaction mixture was cooled The solution was washed with 3N aqueous hydrochloric acid, brine, 1N aqueous sodium hydroxide and brine again was dried over anhydrous magnesium sulfate filtered The filtrate was evaporated in vacuo gave a yellow oil The oil was treated by preparative high pressure liquid chromatography

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

実験手順: To a solution of 1.94 g of 2,4-difluoroaniline in 20 ml of toluene was added dropwise 1.29 g of phenyl chloroformate. The mixture was stirred for 15 minutes, washed with three 10 ml portions of water, dried over anhydrous sodium sulfate, and filtered through a pad of diatomaceous earth. The filtrate was evaporated in vacuo to give an oil which solidified on cooling. The solid was crystallized from hexane to give 1.73 g of the desired product as pale tan crystals in 93% yield, mp 82°-84° C. washed with three 10 ml portions of water dried over anhydrous sodium sulfate filtered through a pad of diatomaceous earth The filtrate was evaporated in vacuo to give an oil which on cooling The solid was crystallized from hexane

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

実験手順: The intermediate is then reacted with a secondary amine in an aprotic solvent such as toluene at temperatures from room temperature or below up to the boiling point of the solvent. An example of this process is the reaction of 2,4-difluoroaniline with phenyl chloroformate to yield the intermediate phenyl N-(2,4-difluorophenyl)carbamate which is then reacted with N-(4-butylphenyl)-N-(6-hydroxyhexyl)amine to yield 1-(4-n-butylphenyl)-3-(2,4-difluorophenyl)-1-(6-hydroxyhexyl)urea.

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Phenyl 2,4-difluorophenylcarbamate (5.0 g) and 4.2 g of glycine ethyl ester hydrochloride were dissolved in 30 ml of pyridine and the solution was heated at 80° C. for 14 hours. The reaction solution was concentrated under reduced pressure and to the residue were added 80 ml of ethyl acetate and 20 ml of water. The ethyl acetate layer was washed with 10 ml of an aqueous solution of sodium chloride, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. Hexane (50 ml) was added to the residue and the solid separated out was collected by filtration to give 4.58 g of N-(2,4-difluorophenyl)-N'-ethoxycarbonylmethylurea as a colorless powder. The reaction solution was concentrated under reduced pressure and to the residue were added 80 ml of ethyl acetate and 20 ml of water The ethyl acetate layer was washed with 10 ml of an aqueous solution of sodium chloride dried over anhydrous magnesium sulfate concentrated under reduced pressure Hexane (50 ml) was added to the residue the solid separated out was collected by filtration

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Phenyl 2,4-difluorophenylcarbamate (5.0 g) and 4.2 g of glycine ethyl ester hydrochloride were dissolved in 30 ml of pyridine and the solution was heated at 80° C. for 14 hours. The reaction solution was concentrated under reduced pressure and to the residue were added 80 ml of ethyl acetate and 20 ml of water. The ethyl acetate layer was washed with 10 ml of an aqueous solution of sodium chloride, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. Hexane (50 ml) was added to the residue and the solid separated out was collected by filtration to give 4.58 g of N-(2,4-difluorophenyl)-N'-ethoxycarbonylmethylurea as a colorless powder. The reaction solution was concentrated under reduced pressure and to the residue were added 80 ml of ethyl acetate and 20 ml of water The ethyl acetate layer was washed with 10 ml of an aqueous solution of sodium chloride dried over anhydrous magnesium sulfate concentrated under reduced pressure Hexane (50 ml) was added to the residue the solid separated out was collected by filtration

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

実験手順: 2,4-Difluroaniline (25 g) and 25.2 g of pyridine were dissolved in 200 ml of dichloromethane and, with ice cooling, 33.3 g of phenyl chloroformate was added dropwise thereinto. The reaction solution was stirred with ice cooling for 30 minutes, washed with water and dried. The solvent was distilled off to give a mixture of phenyl 2,4-difluorophenylcarbamate and pyridine. To the mixture was added 30.7 g of 2-(diethoxy)ethylamine, and the resulting mixture was stirred at room temperature. The crystals separated out were collected by filtration and washed with petroleum ether to give 37.8 g of N-(2,2-diethoxyethyl)-N'-(2,4-difluorophenyl)urea as colorless crystals. was added dropwise washed with water dried The solvent was distilled off to give the resulting mixture was stirred at room temperature The crystals separated out were collected by filtration washed with petroleum ether

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

実験手順: 2,4-Difluroaniline (25 g) and 25.2 g of pyridine were dissolved in 200 ml of dichloromethane and, with ice cooling, 33.3 g of phenyl chloroformate was added dropwise thereinto. The reaction solution was stirred with ice cooling for 30 minutes, washed with water and dried. The solvent was distilled off to give a mixture of phenyl 2,4-difluorophenylcarbamate and pyridine. To the mixture was added 30.7 g of 2-(diethoxy)ethylamine, and the resulting mixture was stirred at room temperature. The crystals separated out were collected by filtration and washed with petroleum ether to give 37.8 g of N-(2,2-diethoxyethyl)-N'-(2,4-difluorophenyl)urea as colorless crystals. was added dropwise washed with water dried The solvent was distilled off to give the resulting mixture was stirred at room temperature The crystals separated out were collected by filtration washed with petroleum ether