2-(2-氯-3,4-二甲氧基)苯乙胺

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 8.0 g of 2-chloro-3,4-dimethoxy-phenethylamine and 5.25 g of m-trifluoromethyl-α-methoxyphenethylbromide is heated at 100°-105° for 21/2 hours. The product was partitioned betwen ethyl acetate and 5% sodium bicarbonate solution. The organic layer was removed, washed with brine, dried and concentrated. The residue was passed over 350 g of silica gel with 1 to 2 % methanol/chloroform. The resulting product was an oil whose hydrochloride melted at 200°-202° . The oily base (2.5 g.) was heated with 50 ml of 48% hydrogen bromide and worked up as above to give the desired 6-chloro-7,8-dihydroxy-1-(m-trifluoromethylphenyl)-2,3,4,5-tetrahydro-1H-3-benzazepine hydrobromide, m.p. ~250°. is heated at 100°-105° for 21/2 hours The product was partitioned betwen ethyl acetate and 5% sodium bicarbonate solution The organic layer was removed washed with brine dried concentrated The oily base (2.5 g.) was heated with 50 ml of 48% hydrogen bromide

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To the solution of 2-(2-chloro-3,4-dimethoxyphenyl)ethanamine (2.8 g, 12.98 mmol) in dichloromethane (DCM) (40 mL) at 0° C. was added triethylamine (1.990 mL, 14.28 mmol) and ethyl chloroformate (1.371 mL, 14.28 mmol). The reaction mixture was stirred at room temperature for 12 hours. The resulting mixture was washed with water, brine, dried over magnesium sulfate and chromatographed to give ethyl 2-chloro-3,4-dimethoxyphenethylcarbamate (1.7 g, 5.91 mmol, 97% yield). LCMS (M+H)+: 288.1 The resulting mixture was washed with water, brine dried over magnesium sulfate chromatographed

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To the solution of 2-(2-chloro-3,4-dimethoxyphenyl)ethanamine (2.8 g, 12.98 mmol) in dichloromethane (DCM) (40 mL) at 0° C. was added triethylamine (1.990 mL, 14.28 mmol) and ethyl chloroformate (1.371 mL, 14.28 mmol). The reaction mixture was stirred at room temperature for 12 hours. The resulting mixture was washed with water, brine, dried over magnesium sulfate and chromatographed to give ethyl 2-chloro-3,4-dimethoxyphenethylcarbamate (1.7 g, 5.91 mmol, 97% yield). LCMS (M+H)+: 288.1 The resulting mixture was washed with water, brine dried over magnesium sulfate chromatographed

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To tetrahydrofuran (THF) (60 mL) was added lithium aluminum hydride (1.822 g, 48.0 mmol) at 0° C. and aluminium chloride (6.40 g, 48.0 mmol) in tetrahydrofuran (THF) (80 mL) was added via syringe. The solution of (E)-2-chloro-3,4-dimethoxy-1-(2-nitrovinyl)benzene (5.85 g, 24 mmol) in tetrahydrofuran (THF) (100 mL) was added via addition funnel over 40 min. Stirred at rt for 16 h. Water (8 ml) was added dropwise followed by 5N hydrochloric acid (60 ml). The mixture was washed with ether (2×200 mL) and the aqueous phase was made basic with 6N sodium hydroxide. The aqueous layer was extracted with ether (3×200 mL). Dried over magnesium sulfate, evaporated to give 2-(2-chloro-3,4-dimethoxyphenyl)ethanamine (2.85 g, 13.21 mmol, 55.1% yield). LCMS (M+H)+: 216.0 The mixture was washed with ether (2×200 mL) The aqueous layer was extracted with ether (3×200 mL) Dried over magnesium sulfate evaporated

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 16.86 g of (2-chloro-3,4-dimethoxyphenyl)ethylamine obtained in step 4 was reacted with 15.33 g of methyl 4-methoxymandelate obtained in step 5 at 130° to 140° C. in a nitrogen gas atmosphere for 1.5 hour. After cooling, the reaction mixture was dissolved in 30 ml of ethyl acetate and purified by silica gel chromatography. After development with ethyl acetate/n-hexane (1/1) and then with ethyl acetate, 20.6 g (69%) of N-(2-chloro-3,4-dimethoxyphenylethyl)-4-methoxymandelamide was obtained. After cooling purified by silica gel chromatography

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 16.86 g of (2-chloro-3,4-dimethoxyphenyl)ethylamine obtained in step 4 was reacted with 15.33 g of methyl 4-methoxymandelate obtained in step 5 at 130° to 140° C. in a nitrogen gas atmosphere for 1.5 hour. After cooling, the reaction mixture was dissolved in 30 ml of ethyl acetate and purified by silica gel chromatography. After development with ethyl acetate/n-hexane (1/1) and then with ethyl acetate, 20.6 g (69%) of N-(2-chloro-3,4-dimethoxyphenylethyl)-4-methoxymandelamide was obtained. After cooling purified by silica gel chromatography

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 28.8 g of LiAlH4 was dispersed in 920 ml of THF in a nitrogen stream. A solution of 100 g of AlCl3 in 1220 ml of THF was added dropwise to the dispersion under cooling at 0° C. After the completion of the addition, the mixture was stirred for 1 hour and a solution of 92 g of 2-chloro-3,4-dimethoxy-β-nitrostyrene obtained in Step 3 in 1440 ml of THF was added dropwise thereto. After the mixture was stirred at room temperature overnight, 122 ml of water was carefully added dropwise thereto under cooling with ice and then 122 ml of concentrated NH4OH was added dropwise thereto. The mixture was stirred for 1 hour and crystals thus precipitated were separated by filtration and the mother liquor was concentrated under reduced pressure. 300 ml of ethyl acetate and a 10% NaOH aqueous solution were added to the residue to conduct extraction. After washing with water followed by dehydration over MgSO4 and concentration to dryness under reduced pressure, 2-(2-chloro-3,4-dimethoxyphenyl)ethylamine (63.9 g, 79%) was obtained. After the completion of the addition After the mixture was stirred at room temperature overnight under cooling with ice The mixture was stirred for 1 hour crystals thus precipitated were separated by filtration the mother liquor was concentrated under reduced pressure 300 ml of ethyl acetate and a 10% NaOH aqueous solution were added to the residue extraction After washing with water followed by dehydration over MgSO4 and concentration to dryness under reduced pressure

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 8.0 g of 2-chloro-3,4-dimethoxy-phenethylamine and 5.25 g of m-trifluoromethyl-α-methoxy-phenethylbromide is heated at 100°-105° for 21/2 hours. The product was partitioned between ethyl acetate and 5% sodium bicarbonate solution. The organic layer was removed, washed with brine, dried and concentrated. The residue was passed over 350 g of silica gel with 1 to 2% methanol/chloroform. The resulting product was an oil whose hydrochloride melted at 200°-202°. The oily base (2.5 g) was heated with 50 ml of 48% hydrogen bromide and worked up as above to give the desired 6-chloro-7,8-dihydroxy-1-(m-trifluoromethylphenyl)-2,3,4,5-tetrahydro-1H-3-benzazepine hydrobromide, m.p. ~250°. is heated at 100°-105° for 21/2 hours The product was partitioned between ethyl acetate and 5% sodium bicarbonate solution The organic layer was removed washed with brine dried concentrated The oily base (2.5 g) was heated with 50 ml of 48% hydrogen bromide

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 8.0 g of 2-chloro-3,4-dimethoxy-phenethylamine and 5.25 g of m-trifluoromethyl-α-methoxy-phenethylbromide is heated at 100°-105° for 21/2 hours. The product was partitioned between ethyl acetate and 5% sodium bicarbonate solution. The organic layer was removed, washed with brine, dried and concentrated. The residue was passed over 350 g of silica gel with 1 to 2% methanol/chloroform. The resulting product was an oil whose hydrochloride melted at 200°-202°. The oily base (2.5 g) was heated with 50 ml of 48% hydrogen bromide and worked up as above to give the desired 6-chloro-7,8-dihydroxy-1-(m-trifluoromethylphenyl)-2,3,4,5-tetrahydro-1H-3-benzazepine hydrobromide, m.p. ~250°. is heated at 100°-105° for 21/2 hours The product was partitioned between ethyl acetate and 5% sodium bicarbonate solution The organic layer was removed washed with brine dried concentrated The oily base (2.5 g) was heated with 50 ml of 48% hydrogen bromide

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 8.0 g of 2-chloro-3,4-dimethoxy-phenethylamine and 5.25 g of m-trifluoromethyl-α-methoxy-phenethylbromide is heated at 100°-105° for 21/2 hours. The product was partitioned between ethyl acetate and 5% sodium bicarbonate solution. The organic layer was removed, washed with brine, dried and concentrated. The residue was passed over 350 g of silica gel with 1 to 2% methanol/chloroform. The resulting product was an oil whose hydrochloride melted at 200°-202°. The oily base (2.5 g) was heated with 50 ml of 48% hydrogen bromide and worked up as above to give the desired 6-chloro-7,8-dihydroxy-1-(m-trifluoromethylphenyl)-2,3,4,5-tetrahydro-1H-3-benzazepine hydrobromide, m.p. ~250°. is heated at 100°-105° for 21/2 hours The product was partitioned between ethyl acetate and 5% sodium bicarbonate solution The organic layer was removed washed with brine dried concentrated The oily base (2.5 g) was heated with 50 ml of 48% hydrogen bromide

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 8.0 g of 2-chloro-3,4-dimethoxy-phenethylamine and 5.25 g of m-trifluoromethyl-α-methoxyphenethylbromide is heated at 100°-105° for 21/2 hours. The product was partitioned betwen ethyl acetate and 5% sodium bicarbonate solution. The organic layer was removed, washed with brine, dried and concentrated. The residue was passed over 350 g of silica gel with 1 to 2 % methanol/chloroform. The resulting product was an oil whose hydrochloride melted at 200°-202° . The oily base (2.5 g.) was heated with 50 ml of 48% hydrogen bromide and worked up as above to give the desired 6-chloro-7,8-dihydroxy-1-(m-trifluoromethylphenyl)-2,3,4,5-tetrahydro-1H-3-benzazepine hydrobromide, m.p. ~250°. is heated at 100°-105° for 21/2 hours The product was partitioned betwen ethyl acetate and 5% sodium bicarbonate solution The organic layer was removed washed with brine dried concentrated The oily base (2.5 g.) was heated with 50 ml of 48% hydrogen bromide

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To the solution of 2-(2-chloro-3,4-dimethoxyphenyl)ethanamine (2.8 g, 12.98 mmol) in dichloromethane (DCM) (40 mL) at 0° C. was added triethylamine (1.990 mL, 14.28 mmol) and ethyl chloroformate (1.371 mL, 14.28 mmol). The reaction mixture was stirred at room temperature for 12 hours. The resulting mixture was washed with water, brine, dried over magnesium sulfate and chromatographed to give ethyl 2-chloro-3,4-dimethoxyphenethylcarbamate (1.7 g, 5.91 mmol, 97% yield). LCMS (M+H)+: 288.1 The resulting mixture was washed with water, brine dried over magnesium sulfate chromatographed