N-[(2-methoxyphenyl)methyl]benzamide

Conditions: temp:9.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of sodium carbonate (232 g, 2.19 mol) in water (750 mL) were added toluene (750 mL) and water (750 mL), the mixture was cooled to 9° C., and o-methoxybenzylamine (300 g, 2.19 mol) was added thereto. To the mixture was added dropwise benzoyl chloride (307 g, 2.19 mol) with stirring at 3-8° C. During addition dropwise, toluene (750 mL) was added thereto to stir the mixture. The reaction mixture was allowed to warm to room temperature, and stirred for 20 min. The reaction was monitored by TLC (eluent: hexane/ethyl acetate (1:1)). The reaction mixture was cooled to 3° C., and filtered. To the solid was added city water (800 mL), and the mixture was stirred for 7.5 hr, and filtered. The organic layer of the mother liquor was concentrated to dryness. The solid collected by filtration was suspended in toluene (600 mL), the suspension was filtered, and the filtrate was concentrated to dryness. The solid collected by filtration, the residue obtained by concentration to dryness of the organic layer of the above-mentioned mother liquor, the residue obtained by concentration to dryness of the filtrate of the toluene suspension, dichloromethane (1500 mL) and water (1500 mL) were mixed, and the organic layer was separated. The organic layer was washed successively with 1 mol/L hydrochloric acid (600 mL), water (600 mL) and 20% brine (600 mL), and dried over magnesium sulfate (60 g). The magnesium sulfate was filtered off, and the filtrate was concentrated under reduced pressure in a bath at 50° C. or lower (about 830 g), and the bath temperature was decreased to 18° C. The solid was collected by filtration, washed with cold dichloromethane (85 mL), and dried under reduced pressure at 50° C. or lower to give N-benzoyl-2-methoxybenzylamine (the primary crystals 481 g, 91.2%) as white crystals. As a result of HPLC analysis, the area percentage was 99.3%, and the content was 97.8%. During addition dropwise to stir the mixture to warm to room temperature stirred for 20 min The reaction mixture was cooled to 3° C. filtered To the solid was added city water (800 mL) the mixture was stirred for 7.5 hr filtered The organic layer of the mother liquor was concentrated to dryness The solid collected by filtration the suspension was filtered the filtrate was concentrated to dryness The solid collected by filtration the residue obtained by concentration to dryness of the organic layer of the above-mentioned mother liquor were mixed the organic layer was separated The organic layer was washed successively with 1 mol/L hydrochloric acid (600 mL), water (600 mL) and 20% brine (600 mL) dried over magnesium sulfate (60 g) The magnesium sulfate was filtered off the filtrate was concentrated under reduced pressure in a bath at 50° C. was decreased to 18° C The solid was collected by filtration washed with cold dichloromethane (85 mL) dried under reduced pressure at 50° C.

Conditions: temp:16.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixture of o-methoxybenzylamine (20.0 g, 0.146 mol), tetrahydrofuran (124 mL) and triethylamine (15.6 g, 0.154 mol) was added dropwise benzoyl chloride (20.5 g, 0.146 mol) at −9-0° C., and the dropping funnel was washed with THF (10 mL). Under a nitrogen atmosphere, the reaction mixture was gradually warmed to about 16° C. During warming, THF (total 51 ml) was appropriately added to stir the content. The reaction was confirmed by TLC (eluent: hexane/ethyl acetate (1:1)). The reaction mixture was stirred at about 16° C. for 10 hr, and cooled to 5° C. Water (44 ml) was added thereto, and the mixture was extracted three times with ethyl acetate (120 mL, 40 mL, 40 mL). The combined organic layers were washed successively with 10% hydrochloric acid (40 mL), saturated aqueous sodium hydrogen carbonate solution (40 mL), water (40 mL) and saturated brine (44 mL), and dried over magnesium sulfate (20 g), and the solvent was evaporated under reduced pressure at 40° C. or lower. Ethyl acetate was added to the residue (content 74 g), and the solid was dissolved with heating to 60° C. The solution was gradually cooled to 6° C., the precipitated crystals were collected by filtration, washed with cold ethyl acetate (10 mL), and dried under reduced pressure at 40° C. or lower to give N-benzoyl-2-methoxybenzylamine (30.7 g, 87.1%) as white crystals. the dropping funnel was washed with THF (10 mL) During warming THF (total 51 ml) was appropriately added The reaction mixture was stirred at about 16° C. for 10 hr cooled to 5° C Water (44 ml) was added the mixture was extracted three times with ethyl acetate (120 mL, 40 mL, 40 mL) The combined organic layers were washed successively with 10% hydrochloric acid (40 mL), saturated aqueous sodium hydrogen carbonate solution (40 mL), water (40 mL) and saturated brine (44 mL) dried over magnesium sulfate (20 g) the solvent was evaporated under reduced pressure at 40° C. Ethyl acetate was added to the residue (content 74 g) the solid was dissolved with heating to 60° C The solution was gradually cooled to 6° C. the precipitated crystals were collected by filtration washed with cold ethyl acetate (10 mL) dried under reduced pressure at 40° C.

Conditions: temp:9.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of sodium carbonate (232 g, 2.19 mol) in water (750 mL) were added toluene (750 mL) and water (750 mL), the mixture was cooled to 9° C., and o-methoxybenzylamine (300 g, 2.19 mol) was added thereto. To the mixture was added dropwise benzoyl chloride (307 g, 2.19 mol) with stirring at 3-8° C. During addition dropwise, toluene (750 mL) was added thereto to stir the mixture. The reaction mixture was allowed to warm to room temperature, and stirred for 20 min. The reaction was monitored by TLC (eluent: hexane/ethyl acetate (1:1)). The reaction mixture was cooled to 3° C., and filtered. To the solid was added city water (800 mL), and the mixture was stirred for 7.5 hr, and filtered. The organic layer of the mother liquor was concentrated to dryness. The solid collected by filtration was suspended in toluene (600 mL), the suspension was filtered, and the filtrate was concentrated to dryness. The solid collected by filtration, the residue obtained by concentration to dryness of the organic layer of the above-mentioned mother liquor, the residue obtained by concentration to dryness of the filtrate of the toluene suspension, dichloromethane (1500 mL) and water (1500 mL) were mixed, and the organic layer was separated. The organic layer was washed successively with 1 mol/L hydrochloric acid (600 mL), water (600 mL) and 20% brine (600 mL), and dried over magnesium sulfate (60 g). The magnesium sulfate was filtered off, and the filtrate was concentrated under reduced pressure in a bath at 50° C. or lower (about 830 g), and the bath temperature was decreased to 18° C. The solid was collected by filtration, washed with cold dichloromethane (85 mL), and dried under reduced pressure at 50° C. or lower to give N-benzoyl-2-methoxybenzylamine (the primary crystals 481 g, 91.2%) as white crystals. As a result of HPLC analysis, the area percentage was 99.3%, and the content was 97.8%. During addition dropwise to stir the mixture to warm to room temperature stirred for 20 min The reaction mixture was cooled to 3° C. filtered To the solid was added city water (800 mL) the mixture was stirred for 7.5 hr filtered The organic layer of the mother liquor was concentrated to dryness The solid collected by filtration the suspension was filtered the filtrate was concentrated to dryness The solid collected by filtration the residue obtained by concentration to dryness of the organic layer of the above-mentioned mother liquor were mixed the organic layer was separated The organic layer was washed successively with 1 mol/L hydrochloric acid (600 mL), water (600 mL) and 20% brine (600 mL) dried over magnesium sulfate (60 g) The magnesium sulfate was filtered off the filtrate was concentrated under reduced pressure in a bath at 50° C. was decreased to 18° C The solid was collected by filtration washed with cold dichloromethane (85 mL) dried under reduced pressure at 50° C.

Conditions: temp:16.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixture of o-methoxybenzylamine (20.0 g, 0.146 mol), tetrahydrofuran (124 mL) and triethylamine (15.6 g, 0.154 mol) was added dropwise benzoyl chloride (20.5 g, 0.146 mol) at −9-0° C., and the dropping funnel was washed with THF (10 mL). Under a nitrogen atmosphere, the reaction mixture was gradually warmed to about 16° C. During warming, THF (total 51 ml) was appropriately added to stir the content. The reaction was confirmed by TLC (eluent: hexane/ethyl acetate (1:1)). The reaction mixture was stirred at about 16° C. for 10 hr, and cooled to 5° C. Water (44 ml) was added thereto, and the mixture was extracted three times with ethyl acetate (120 mL, 40 mL, 40 mL). The combined organic layers were washed successively with 10% hydrochloric acid (40 mL), saturated aqueous sodium hydrogen carbonate solution (40 mL), water (40 mL) and saturated brine (44 mL), and dried over magnesium sulfate (20 g), and the solvent was evaporated under reduced pressure at 40° C. or lower. Ethyl acetate was added to the residue (content 74 g), and the solid was dissolved with heating to 60° C. The solution was gradually cooled to 6° C., the precipitated crystals were collected by filtration, washed with cold ethyl acetate (10 mL), and dried under reduced pressure at 40° C. or lower to give N-benzoyl-2-methoxybenzylamine (30.7 g, 87.1%) as white crystals. the dropping funnel was washed with THF (10 mL) During warming THF (total 51 ml) was appropriately added The reaction mixture was stirred at about 16° C. for 10 hr cooled to 5° C Water (44 ml) was added the mixture was extracted three times with ethyl acetate (120 mL, 40 mL, 40 mL) The combined organic layers were washed successively with 10% hydrochloric acid (40 mL), saturated aqueous sodium hydrogen carbonate solution (40 mL), water (40 mL) and saturated brine (44 mL) dried over magnesium sulfate (20 g) the solvent was evaporated under reduced pressure at 40° C. Ethyl acetate was added to the residue (content 74 g) the solid was dissolved with heating to 60° C The solution was gradually cooled to 6° C. the precipitated crystals were collected by filtration washed with cold ethyl acetate (10 mL) dried under reduced pressure at 40° C.

Conditions: temp:9.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of sodium carbonate (232 g, 2.19 mol) in water (750 mL) were added toluene (750 mL) and water (750 mL), the mixture was cooled to 9° C., and o-methoxybenzylamine (300 g, 2.19 mol) was added thereto. To the mixture was added dropwise benzoyl chloride (307 g, 2.19 mol) with stirring at 3-8° C. During addition dropwise, toluene (750 mL) was added thereto to stir the mixture. The reaction mixture was allowed to warm to room temperature, and stirred for 20 min. The reaction was monitored by TLC (eluent: hexane/ethyl acetate (1:1)). The reaction mixture was cooled to 3° C., and filtered. To the solid was added city water (800 mL), and the mixture was stirred for 7.5 hr, and filtered. The organic layer of the mother liquor was concentrated to dryness. The solid collected by filtration was suspended in toluene (600 mL), the suspension was filtered, and the filtrate was concentrated to dryness. The solid collected by filtration, the residue obtained by concentration to dryness of the organic layer of the above-mentioned mother liquor, the residue obtained by concentration to dryness of the filtrate of the toluene suspension, dichloromethane (1500 mL) and water (1500 mL) were mixed, and the organic layer was separated. The organic layer was washed successively with 1 mol/L hydrochloric acid (600 mL), water (600 mL) and 20% brine (600 mL), and dried over magnesium sulfate (60 g). The magnesium sulfate was filtered off, and the filtrate was concentrated under reduced pressure in a bath at 50° C. or lower (about 830 g), and the bath temperature was decreased to 18° C. The solid was collected by filtration, washed with cold dichloromethane (85 mL), and dried under reduced pressure at 50° C. or lower to give N-benzoyl-2-methoxybenzylamine (the primary crystals 481 g, 91.2%) as white crystals. As a result of HPLC analysis, the area percentage was 99.3%, and the content was 97.8%. During addition dropwise to stir the mixture to warm to room temperature stirred for 20 min The reaction mixture was cooled to 3° C. filtered To the solid was added city water (800 mL) the mixture was stirred for 7.5 hr filtered The organic layer of the mother liquor was concentrated to dryness The solid collected by filtration the suspension was filtered the filtrate was concentrated to dryness The solid collected by filtration the residue obtained by concentration to dryness of the organic layer of the above-mentioned mother liquor were mixed the organic layer was separated The organic layer was washed successively with 1 mol/L hydrochloric acid (600 mL), water (600 mL) and 20% brine (600 mL) dried over magnesium sulfate (60 g) The magnesium sulfate was filtered off the filtrate was concentrated under reduced pressure in a bath at 50° C. was decreased to 18° C The solid was collected by filtration washed with cold dichloromethane (85 mL) dried under reduced pressure at 50° C.

Conditions: temp:16.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixture of o-methoxybenzylamine (20.0 g, 0.146 mol), tetrahydrofuran (124 mL) and triethylamine (15.6 g, 0.154 mol) was added dropwise benzoyl chloride (20.5 g, 0.146 mol) at −9-0° C., and the dropping funnel was washed with THF (10 mL). Under a nitrogen atmosphere, the reaction mixture was gradually warmed to about 16° C. During warming, THF (total 51 ml) was appropriately added to stir the content. The reaction was confirmed by TLC (eluent: hexane/ethyl acetate (1:1)). The reaction mixture was stirred at about 16° C. for 10 hr, and cooled to 5° C. Water (44 ml) was added thereto, and the mixture was extracted three times with ethyl acetate (120 mL, 40 mL, 40 mL). The combined organic layers were washed successively with 10% hydrochloric acid (40 mL), saturated aqueous sodium hydrogen carbonate solution (40 mL), water (40 mL) and saturated brine (44 mL), and dried over magnesium sulfate (20 g), and the solvent was evaporated under reduced pressure at 40° C. or lower. Ethyl acetate was added to the residue (content 74 g), and the solid was dissolved with heating to 60° C. The solution was gradually cooled to 6° C., the precipitated crystals were collected by filtration, washed with cold ethyl acetate (10 mL), and dried under reduced pressure at 40° C. or lower to give N-benzoyl-2-methoxybenzylamine (30.7 g, 87.1%) as white crystals. the dropping funnel was washed with THF (10 mL) During warming THF (total 51 ml) was appropriately added The reaction mixture was stirred at about 16° C. for 10 hr cooled to 5° C Water (44 ml) was added the mixture was extracted three times with ethyl acetate (120 mL, 40 mL, 40 mL) The combined organic layers were washed successively with 10% hydrochloric acid (40 mL), saturated aqueous sodium hydrogen carbonate solution (40 mL), water (40 mL) and saturated brine (44 mL) dried over magnesium sulfate (20 g) the solvent was evaporated under reduced pressure at 40° C. Ethyl acetate was added to the residue (content 74 g) the solid was dissolved with heating to 60° C The solution was gradually cooled to 6° C. the precipitated crystals were collected by filtration washed with cold ethyl acetate (10 mL) dried under reduced pressure at 40° C.