2-amino-5-methoxy-4-phenylmethoxybenzonitrile

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

実験手順: 2-amino-4-benzyloxy-5-methoxy benzonitrile (102 g, 400 mmol) in toluene (1.51) was reacted with DMF-DMA (110 ml, 780 mmol) at reflux for 5 hours. The solvent was evaporated, the residue triturated with ether to give title compound as yellow solid. at reflux for 5 hours The solvent was evaporated the residue triturated with ether

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

実験手順: 2-amino-4-benzyloxy-5-methoxy benzonitrile (102 g, 400 mmol) in toluene (1.51) was reacted with DMF-DMA (110 ml, 780 mmol) at reflux for 5 hours. The solvent was evaporated, the residue triturated with ether to give title compound as yellow solid. at reflux for 5 hours The solvent was evaporated the residue triturated with ether

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

実験手順: 2-nitro-4-benzyloxy-5-methoxybenzonitrile (40 g, 125 mmol) tetrabutylammonium chloride (21 g, 75 mmol) in methylenechloride (500 ml) was treated with Na2S2O4 (180 g, 87.9 mmol) in H2O (700 ml), sodium hydrosulfite was added over 45 minutes, and the mixture was stirred for 2 hours at room temperature. Sodium hydroxyde was added (pH 8.2) the mixture was extracted with methylene chloride. The organic phase was made acidic with HCl-ether (2.3N, 250 ml), the solid was recovered, suspended in methanol (250 ml) and treated with a saturated solution of sodium bicarbonate (pH 8.1). The solid was recovered, washed with water, ether to give title compound (30.7 g, 97%). was added over 45 minutes was extracted with methylene chloride the solid was recovered treated with a saturated solution of sodium bicarbonate (pH 8.1) The solid was recovered washed with water, ether

反応条件: temp:105.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2-amino-4-(benzyloxy)-5-methoxybenzonitrile (100 g, 394 mmol) in toluene (1400 ml) was treated with dimethylformamide dimethylacetal (100 ml, 940 mmol) at reflux with slow distillation of solvent to maintain the internal temperature at 105° C. After 3 hours the solution was cooled and filtered to remove a small amount of solid. The filtrate was evaporated in vacuo, the residue triturated with diethyl ether, the solid collected by suction filtration and dried in vacuo to yield N′-(5-(benzyloxy)-2-cyano-4-methoxyphenyl)-N,N-dimethylimidoformamide (110 g, 90% yield) as a brown solid: at reflux with slow distillation of solvent After 3 hours the solution was cooled filtered to remove a small amount of solid The filtrate was evaporated in vacuo the residue triturated with diethyl ether the solid collected by suction filtration dried in vacuo

反応条件: temp:105.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2-amino-4-(benzyloxy)-5-methoxybenzonitrile (100 g, 394 mmol) in toluene (1400 ml) was treated with dimethylformamide dimethylacetal (100 ml, 940 mmol) at reflux with slow distillation of solvent to maintain the internal temperature at 105° C. After 3 hours the solution was cooled and filtered to remove a small amount of solid. The filtrate was evaporated in vacuo, the residue triturated with diethyl ether, the solid collected by suction filtration and dried in vacuo to yield N′-(5-(benzyloxy)-2-cyano-4-methoxyphenyl)-N,N-dimethylimidoformamide (110 g, 90% yield) as a brown solid: at reflux with slow distillation of solvent After 3 hours the solution was cooled filtered to remove a small amount of solid The filtrate was evaporated in vacuo the residue triturated with diethyl ether the solid collected by suction filtration dried in vacuo

反応条件: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 4-benzyloxy-3-methoxy-6-nitrobenzonitrile (46 g, 162 mmol), sodium bicarbonate (95 g, 1.13 mol), water (750 ml), dichloromethane (550 ml) and tetrabutylammonium chloride (30 g, 108 mmol) was rapidly stirred at 20° C. and treated portionwise with sodium dithionite (66 g, 379 mmol) over 2 hours. The mixture was stirred for a further 1 hour then the phases separated. The aqueous phase was extracted with dichloromethane (2×200 ml) and the combined organic solution washed with water (300 ml) and dried over magnesium sulphate. The solution was concentrated to 250 ml and 4.0 N hydrochloric acid in 1,4-dioxane (150 ml, 0.6 mol) added. The reaction was then diluted with diethyl ether (1000 ml) and cooled on ice. The resulting solid was collected by suction filtration and washed with diethyl ether. The solid was stirred in methanol (1000 ml) and sodium bicarbonate solution (800 ml) added (pH 8) and the mixture stirred for 1 hour. The solid was collected by suction filtration, washed with water, methanol and dried in vacuo to yield 2-amino-4-(benzyloxy)-5-methoxybenzonitrile (34 g, 82% yield) as light brown solid: The mixture was stirred for a further 1 hour the phases separated The aqueous phase was extracted with dichloromethane (2×200 ml) the combined organic solution washed with water (300 ml) dried over magnesium sulphate added cooled on ice The resulting solid was collected by suction filtration washed with diethyl ether The solid was stirred in methanol (1000 ml) sodium bicarbonate solution (800 ml) added (pH 8) the mixture stirred for 1 hour The solid was collected by suction filtration washed with water, methanol dried in vacuo

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

実験手順: 2-amino-4-benzyloxy-5-methoxy benzonitrile (102 g, 400 mmol) in toluene (1.51) was reacted with DMF-DMA (110 ml, 780 mmol) at reflux for 5 hours. The solvent was evaporated, the residue triturated with ether to give title compound as yellow solid. at reflux for 5 hours The solvent was evaporated the residue triturated with ether

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

実験手順: 2-nitro-4-benzyloxy-5-methoxybenzonitrile (40 g, 125 mmol) tetrabutylammonium chloride (21 g, 75 mmol) in methylenechloride (500 ml) was treated with Na2S2O4 (180 g, 87.9 mmol) in H2O (700 ml), sodium hydrosulfite was added over 45 minutes, and the mixture was stirred for 2 hours at room temperature. Sodium hydroxyde was added (pH 8.2) the mixture was extracted with methylene chloride. The organic phase was made acidic with HCl-ether (2.3N, 250 ml), the solid was recovered, suspended in methanol (250 ml) and treated with a saturated solution of sodium bicarbonate (pH 8.1). The solid was recovered, washed with water, ether to give title compound (30.7 g, 97%). was added over 45 minutes was extracted with methylene chloride the solid was recovered treated with a saturated solution of sodium bicarbonate (pH 8.1) The solid was recovered washed with water, ether

反応条件: temp:105.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2-amino-4-(benzyloxy)-5-methoxybenzonitrile (100 g, 394 mmol) in toluene (1400 ml) was treated with dimethylformamide dimethylacetal (100 ml, 940 mmol) at reflux with slow distillation of solvent to maintain the internal temperature at 105° C. After 3 hours the solution was cooled and filtered to remove a small amount of solid. The filtrate was evaporated in vacuo, the residue triturated with diethyl ether, the solid collected by suction filtration and dried in vacuo to yield N′-(5-(benzyloxy)-2-cyano-4-methoxyphenyl)-N,N-dimethylimidoformamide (110 g, 90% yield) as a brown solid: at reflux with slow distillation of solvent After 3 hours the solution was cooled filtered to remove a small amount of solid The filtrate was evaporated in vacuo the residue triturated with diethyl ether the solid collected by suction filtration dried in vacuo

反応条件: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 4-benzyloxy-3-methoxy-6-nitrobenzonitrile (46 g, 162 mmol), sodium bicarbonate (95 g, 1.13 mol), water (750 ml), dichloromethane (550 ml) and tetrabutylammonium chloride (30 g, 108 mmol) was rapidly stirred at 20° C. and treated portionwise with sodium dithionite (66 g, 379 mmol) over 2 hours. The mixture was stirred for a further 1 hour then the phases separated. The aqueous phase was extracted with dichloromethane (2×200 ml) and the combined organic solution washed with water (300 ml) and dried over magnesium sulphate. The solution was concentrated to 250 ml and 4.0 N hydrochloric acid in 1,4-dioxane (150 ml, 0.6 mol) added. The reaction was then diluted with diethyl ether (1000 ml) and cooled on ice. The resulting solid was collected by suction filtration and washed with diethyl ether. The solid was stirred in methanol (1000 ml) and sodium bicarbonate solution (800 ml) added (pH 8) and the mixture stirred for 1 hour. The solid was collected by suction filtration, washed with water, methanol and dried in vacuo to yield 2-amino-4-(benzyloxy)-5-methoxybenzonitrile (34 g, 82% yield) as light brown solid: The mixture was stirred for a further 1 hour the phases separated The aqueous phase was extracted with dichloromethane (2×200 ml) the combined organic solution washed with water (300 ml) dried over magnesium sulphate added cooled on ice The resulting solid was collected by suction filtration washed with diethyl ether The solid was stirred in methanol (1000 ml) sodium bicarbonate solution (800 ml) added (pH 8) the mixture stirred for 1 hour The solid was collected by suction filtration washed with water, methanol dried in vacuo