2-iodo-N-methylbenzamide

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Thionyl chloride (29.4 mL, 404 mmol) is added to a solution of (2-iodo-benzoic acid (50.0 g, 202 mmol) in dry toluene (600 mL). The mixture is heated to reflux for 4 hours and the solvent is removed in vacuo. The remanence is redissolved in dry toluene (600 mL) and cooled to 0° C. 40% methylamine (aq., 94.1 mL, 1.21 mol) is added dropwise at 0-5° C. during 30 minutes. The mixture is then stirred at ambient temperature for 16 hours, poured onto water (300 mL) and extracted with ethyl acetate (3×300 mL) The combined organic fractions are washed successively with saturated sodium bicarbonate solution (250 mL) and brine (250 mL), dried (MgSO4) and concentrated in vacuo. This gives 50.8 g (96%) of crystalline 2-iodo-N-methyl-benzamide. The mixture is heated to reflux for 4 hours the solvent is removed in vacuo The remanence is redissolved in dry toluene (600 mL) poured onto water (300 mL) extracted with ethyl acetate (3×300 mL) The combined organic fractions are washed successively with saturated sodium bicarbonate solution (250 mL) and brine (250 mL) dried (MgSO4) concentrated in vacuo

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Thionyl chloride (29.4 mL, 404 mmol) is added to a solution of (2-iodo-benzoic acid (50.0 g, 202 mmol) in dry toluene (600 mL). The mixture is heated to reflux for 4 hours and the solvent is removed in vacuo. The remanence is redissolved in dry toluene (600 mL) and cooled to 0° C. 40% methylamine (aq., 94.1 mL, 1.21 mol) is added dropwise at 0-5° C. during 30 minutes. The mixture is then stirred at ambient temperature for 16 hours, poured onto water (300 mL) and extracted with ethyl acetate (3×300 mL) The combined organic fractions are washed successively with saturated sodium bicarbonate solution (250 mL) and brine (250 mL), dried (MgSO4) and concentrated in vacuo. This gives 50.8 g (96%) of crystalline 2-iodo-N-methyl-benzamide. The mixture is heated to reflux for 4 hours the solvent is removed in vacuo The remanence is redissolved in dry toluene (600 mL) poured onto water (300 mL) extracted with ethyl acetate (3×300 mL) The combined organic fractions are washed successively with saturated sodium bicarbonate solution (250 mL) and brine (250 mL) dried (MgSO4) concentrated in vacuo

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Lithium aluminum hydride (14.8 g, 390 mmol) is suspended in dry diethyl ether (250 mL) and cooled to 0° C. Aluminum chloride (16.0 g, 121 mmol) dissolved in dry diethyl ether (250 mL) is added dropwise at 0-5° C. The cooling bath is removed and the mixture is stirred at ambient temperature for 1 hour. The resulting aluminum hydride reagent solution is cooled to 0° C. followed by dropwise addition of 2-iodo-N-methyl-benzamide (50.8 g, 195 mmol) dissolved in dry THF (500 mL). After complete addition the solution is allowed to heat to ambient temperature and stirring is continued for 16 hours. The mixture is cooled to 10° C. followed by slow dropwise addition of water (30 mL) followed by 2M sodium hydroxide (30 mL) and water (150 mL). MgSO4 is added and the mixture is stirred for 10 minutes, filtered and concentrated in vacuo. The remanence is redissolved in ethyl acetate (500 mL), dried (MgSO4) and concentrated again to furnish 45.2 g (94%) of (2-iodo-benzyl)-methyl-amine as an oil. (2-Iodo-benzyl)-methyl-amine (20.0 g, 80.9 mmol) is dissolved in dry THF (300 mL) and di-tert-butyl dicarbonate (18.5 g, 85.0 mmol) is added. The mixture is stirred for 1 hour at ambient temperature. The volatiles are removed by means of evaporation and the crude mixture is purified by silica gel chromatography eluting with ethyl acetate-heptane (1:4) to furnish 28.5 g (quant.) of the title compound as an oil. is added dropwise at 0-5° C The cooling bath is removed The resulting aluminum hydride reagent solution is cooled to 0° C. After complete addition the solution to heat to ambient temperature stirring is continued for 16 hours The mixture is cooled to 10° C. the mixture is stirred for 10 minutes filtered concentrated in vacuo The remanence is redissolved in ethyl acetate (500 mL) dried (MgSO4) concentrated again

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

実験手順: A total of 40 ml of a 40% by weight aqueous solution of methylamine was reacted with a solution of 16 g of o-iodobenzoyl chloride in 25 ml of tetrahydrofuran for 10 minutes. The excess solvent was evaporated in a hot water bath at 65°. The mixture was allowed to cool and 40 ml of water was added to precipitate the crude product which was recovered and washed with 1 N NaOH, 1 N HCl, and then water until the washings were neutral. The crude product was dried under vacuum and purified by recrystallization from toluene to yield 12.6 g of N-methyl-o-iodobenzamide as white crystals, m.p. 153°-154°, Rf 0.75 on thin layer chromatography using silica gel 60 and methanolchloroform-acetic acid (15:85:1) mixture. The excess solvent was evaporated in a hot water bath at 65° to cool 40 ml of water was added to precipitate the crude product which was recovered washed with 1 N NaOH, 1 N HCl The crude product was dried under vacuum purified by recrystallization from toluene

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Thionyl chloride (29.4 mL, 404 mmol) is added to a solution of (2-iodo-benzoic acid (50.0 g, 202 mmol) in dry toluene (600 mL). The mixture is heated to reflux for 4 hours and the solvent is removed in vacuo. The remanence is redissolved in dry toluene (600 mL) and cooled to 0° C. 40% methylamine (aq., 94.1 mL, 1.21 mol) is added dropwise at 0-5° C. during 30 minutes. The mixture is then stirred at ambient temperature for 16 hours, poured onto water (300 mL) and extracted with ethyl acetate (3×300 mL) The combined organic fractions are washed successively with saturated sodium bicarbonate solution (250 mL) and brine (250 mL), dried (MgSO4) and concentrated in vacuo. This gives 50.8 g (96%) of crystalline 2-iodo-N-methyl-benzamide. The mixture is heated to reflux for 4 hours the solvent is removed in vacuo The remanence is redissolved in dry toluene (600 mL) poured onto water (300 mL) extracted with ethyl acetate (3×300 mL) The combined organic fractions are washed successively with saturated sodium bicarbonate solution (250 mL) and brine (250 mL) dried (MgSO4) concentrated in vacuo

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Lithium aluminum hydride (14.8 g, 390 mmol) is suspended in dry diethyl ether (250 mL) and cooled to 0° C. Aluminum chloride (16.0 g, 121 mmol) dissolved in dry diethyl ether (250 mL) is added dropwise at 0-5° C. The cooling bath is removed and the mixture is stirred at ambient temperature for 1 hour. The resulting aluminum hydride reagent solution is cooled to 0° C. followed by dropwise addition of 2-iodo-N-methyl-benzamide (50.8 g, 195 mmol) dissolved in dry THF (500 mL). After complete addition the solution is allowed to heat to ambient temperature and stirring is continued for 16 hours. The mixture is cooled to 10° C. followed by slow dropwise addition of water (30 mL) followed by 2M sodium hydroxide (30 mL) and water (150 mL). MgSO4 is added and the mixture is stirred for 10 minutes, filtered and concentrated in vacuo. The remanence is redissolved in ethyl acetate (500 mL), dried (MgSO4) and concentrated again to furnish 45.2 g (94%) of (2-iodo-benzyl)-methyl-amine as an oil. (2-Iodo-benzyl)-methyl-amine (20.0 g, 80.9 mmol) is dissolved in dry THF (300 mL) and di-tert-butyl dicarbonate (18.5 g, 85.0 mmol) is added. The mixture is stirred for 1 hour at ambient temperature. The volatiles are removed by means of evaporation and the crude mixture is purified by silica gel chromatography eluting with ethyl acetate-heptane (1:4) to furnish 28.5 g (quant.) of the title compound as an oil. is added dropwise at 0-5° C The cooling bath is removed The resulting aluminum hydride reagent solution is cooled to 0° C. After complete addition the solution to heat to ambient temperature stirring is continued for 16 hours The mixture is cooled to 10° C. the mixture is stirred for 10 minutes filtered concentrated in vacuo The remanence is redissolved in ethyl acetate (500 mL) dried (MgSO4) concentrated again