N-methyl-3-phenylpropan-1-amine

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (2R)-2-(N-(tert-Butoxycarbonyl)-N-methylamino)-3-(2-naphthyl)propionic acid (2.21 g, 6.70 mmol) was dissolved in N,N-dimethylformamide (3 ml) and dichloromethane (6 ml). 1-Hydroxy-7-azabenzotriazole (0.91 g, 6.70 mmol) was added. The solution was cooled to 0° C. N-(3-Dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (1.28 g, 6.70 mmol) was added. The reaction mixture was stirred for 15 min at 0° C. A solution of N-methyl-N-(3-phenylpropyl)amine (1.0 g, 6.7 mmol) in dichloromethane (3 ml) was added. Ethyldiisopropylamine (1.2 ml, 6.7 mmol) was added. The reaction mixture was stirred for 16 h, while it was slowly warming up to room temperature. The solution was diluted with ethyl acetate (100 ml). It was washed with 1 N hydrochloric acid (100 ml). The aqueous phase was extracted with ethyl acetate (100 ml). The combined organic layers were washed with saturated sodium hydrogen carbonate solution (100 ml) and dried over magnesium sulfate. The solvent was removed in vacuo. The crude product was purified by flash chromatography on silica (400 g), using ethyl acetate/heptane (1:3) as eluent to give 1.43 g of N-methyl-N-((1R)-1-(N-methyl-N-(3-phenylpropyl)carbamoyl)-2-(2-naphthyl)ethyl)carbamic acid tert-butyl ester. The reaction mixture was stirred for 16 h, while it was slowly warming up to room temperature It was washed with 1 N hydrochloric acid (100 ml) The aqueous phase was extracted with ethyl acetate (100 ml) The combined organic layers were washed with saturated sodium hydrogen carbonate solution (100 ml) dried over magnesium sulfate The solvent was removed in vacuo The crude product was purified by flash chromatography on silica (400 g)

Conditions: temp:7.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: N-(3-Phenylpropyl)formamide (5.70 g, 34.9 mmol) was dissolved in tetrahydrofuran (50 ml) and added dropwise to a suspension of sodium borohydride (1.58 g, 41.91 mmol) in tetrahydrofuran (100 ml), which was cooled to 7° C. A solution of iodine (4.42 g, 17.46 mmol) in tetrahydrofuran was added dropwise, while the temperature was kept at 7° C. After the addition was finished, the reaction mixture was warmed to reflux for 16 h. The reaction mixture was cooled to 7° C., and methanol (250 ml) was added dropwise. The solvent was removed in vacuo. The residue was dissolved in 20% aqueous sodium hydroxide solution (250 ml) and tert-butyl methyl ether (100 ml). The phases were separated. The aqueous phase was extracted with tert-butyl methyl ether (2×100 ml). The combined organic layers were dried over magnesium sulfate. The solvent was removed in vacuo. The crude product was purified by flash chromatography on silica (400 g), using dichloromethane/methanol/25% aqueous ammonia (100:10:1) as eluent to give 2.76 g of N-methyl-N-(3-phenylpropyl)amine. was kept at 7° C After the addition the reaction mixture was warmed to reflux for 16 h The reaction mixture was cooled to 7° C. The solvent was removed in vacuo The residue was dissolved in 20% aqueous sodium hydroxide solution (250 ml) The phases were separated The aqueous phase was extracted with tert-butyl methyl ether (2×100 ml) The combined organic layers were dried over magnesium sulfate The solvent was removed in vacuo The crude product was purified by flash chromatography on silica (400 g)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (2R)-2-(N-(tert-Butoxycarbonyl)-N-methylamino)-3(2-naphthyl)propionic acid (2.21 g, 6.70 mmol) was dissolved in N,N-dimethylformamide (3 ml) and dichloromethane (6 ml). 1-Hydroxy-7-azabenzotrazole (0.91 g, 6.70 mmol) was added. The solution was cooled to 0° C. N-(3-Dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (1.28 g, 6.70 mmol) was added. The reaction mixture was stirred for 15 min at 0° C. A solution of N-methyl-N-(3-phenylpropyl)amine (1.0 g, 6.7 mmol) in dichloromethane (3 ml) was added. Ethyldiisopropylamine (1.2 ml, 6.7 mmol) was added. The reaction mixture was stirred for 16 h, while it was slowly warming up to room temperature. The solution was diluted with ethyl acetate (100 ml). It was washed with 1 N hydrochloric acid (100 ml). The aqueous phase was extracted with ethyl acetate (100 ml). The combined organic layers were washed with saturated sodium hydrogen carbonate solution (100 ml) and dried over magnesium sulfate. Thesolvent was removed in vacuo. The crude product was purified by flash chromatography on silica (400 g), using ethyl acetateiheptane (1:3) as eluent to give 1.43 g of N-methyl-N-((1R)-1-(N-methyl-N-(3-phenylpropyl)carbamoyl)-2-(2-naphthyl)ethyl)carbamic acid tert-butyl ester. 1-Hydroxy-7-azabenzotrazole (0.91 g, 6.70 mmol) was added The reaction mixture was stirred for 16 h, while it was slowly warming up to room temperature It was washed with 1 N hydrochloric acid (100 ml) The aqueous phase was extracted with ethyl acetate (100 ml) The combined organic layers were washed with saturated sodium hydrogen carbonate solution (100 ml) dried over magnesium sulfate Thesolvent was removed in vacuo The crude product was purified by flash chromatography on silica (400 g)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (2R)-2-(N-(tert-Butoxycarbonyl)-N-methylamino)-3(2-naphthyl)propionic acid (2.21 g, 6.70 mmol) was dissolved in N,N-dimethylformamide (3 ml) and dichloromethane (6 ml). 1-Hydroxy-7-azabenzotrazole (0.91 g, 6.70 mmol) was added. The solution was cooled to 0° C. N-(3-Dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (1.28 g, 6.70 mmol) was added. The reaction mixture was stirred for 15 min at 0° C. A solution of N-methyl-N-(3-phenylpropyl)amine (1.0 g, 6.7 mmol) in dichloromethane (3 ml) was added. Ethyldiisopropylamine (1.2 ml, 6.7 mmol) was added. The reaction mixture was stirred for 16 h, while it was slowly warming up to room temperature. The solution was diluted with ethyl acetate (100 ml). It was washed with 1 N hydrochloric acid (100 ml). The aqueous phase was extracted with ethyl acetate (100 ml). The combined organic layers were washed with saturated sodium hydrogen carbonate solution (100 ml) and dried over magnesium sulfate. Thesolvent was removed in vacuo. The crude product was purified by flash chromatography on silica (400 g), using ethyl acetateiheptane (1:3) as eluent to give 1.43 g of N-methyl-N-((1R)-1-(N-methyl-N-(3-phenylpropyl)carbamoyl)-2-(2-naphthyl)ethyl)carbamic acid tert-butyl ester. 1-Hydroxy-7-azabenzotrazole (0.91 g, 6.70 mmol) was added The reaction mixture was stirred for 16 h, while it was slowly warming up to room temperature It was washed with 1 N hydrochloric acid (100 ml) The aqueous phase was extracted with ethyl acetate (100 ml) The combined organic layers were washed with saturated sodium hydrogen carbonate solution (100 ml) dried over magnesium sulfate Thesolvent was removed in vacuo The crude product was purified by flash chromatography on silica (400 g)

Conditions: temp:7.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: N-(3-Phenylpropyl)formamide (5.70 g, 34.9 mmol) was dissolved in tetrahydrofuran (50 ml) and added dropwise to a suspension of sodium borohydride (1.58 g, 41.91 mmol) in tetrahydrofuran (100 ml), which was cooled to 7° C. A solution of iodine (4.42 g, 17.46 mmol) in tetrahydrofuran was added dropwise, while the temperature was kept at 7° C. After the addition was finished, the reaction mixture was warmed to reflux for 16 h. The reaction mixture was cooled to 7° C., and methanol (250 ml) was added dropwise. The solvent was removed in vacuo. The residue was dissolved in 20% aqueous sodium hydroxide solution (250 ml) and tert-butyl methyl ether (100 ml). The phases were separated. The aqueous phase was extracted with tert-butyl methyl ether (2×100 ml). The combined organic layers were dried over magnesium sulfate. The solvent was removed in vacuo. The crude product was purified by flash chromatography on silica (400 g), using dichicromethane/methanol/25% aqueous ammonia (100:10:1) as eluent to give 2.76 g of N-methyl-N-(3-phenylpropyl)amine. was kept at 7° C After the addition the reaction mixture was warmed to reflux for 16 h The reaction mixture was cooled to 7° C. The solvent was removed in vacuo The residue was dissolved in 20% aqueous sodium hydroxide solution (250 ml) The phases were separated The aqueous phase was extracted with tert-butyl methyl ether (2×100 ml) The combined organic layers were dried over magnesium sulfate The solvent was removed in vacuo The crude product was purified by flash chromatography on silica (400 g)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (2R)-2-(N-(tert-Butoxycarbonyl)-N-methylamino)-3-(2-naphthyl)propionic acid (2.21 g, 6.70 mmol) was dissolved in N,N-dimethylformamide (3 ml) and dichloromethane (6 ml). 1-Hydroxy-7-azabenzotriazole (0.91 g, 6.70 mmol) was added. The solution was cooled to 0° C. N-(3-Dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (1.28 g, 6.70 mmol) was added. The reaction mixture was stirred for 15 min at 0° C. A solution of N-methyl-N-(3-phenylpropyl)amine (1.0 g, 6.7 mmol) in dichloromethane (3 ml) was added. Ethyldiisopropylamine (1.2 ml, 6.7 mmol) was added. The reaction mixture was stirred for 16 h, while it was slowly warming up to room temperature. The solution was diluted with ethyl acetate (100 ml). It was washed with 1 N hydrochloric acid (100 ml). The aqueous phase was extracted with ethyl acetate (100 ml). The combined organic layers were washed with saturated sodium hydrogen carbonate solution (100 ml) and dried over magnesium sulfate. The solvent was removed in vacuo. The crude product was purified by flash chromatography on silica (400 g), using ethyl acetate/heptane (1:3) as eluent to give 1.43 g of N-methyl-N-((1R)-1-(N-methyl-N-(3-phenylpropyl)carbamoyl)-2-(2-naphthyl)ethyl)carbamic acid tert-butyl ester. The reaction mixture was stirred for 16 h, while it was slowly warming up to room temperature It was washed with 1 N hydrochloric acid (100 ml) The aqueous phase was extracted with ethyl acetate (100 ml) The combined organic layers were washed with saturated sodium hydrogen carbonate solution (100 ml) dried over magnesium sulfate The solvent was removed in vacuo The crude product was purified by flash chromatography on silica (400 g)

Conditions: temp:7.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: N-(3-Phenylpropyl)formamide (5.70 g, 34.9 mmol) was dissolved in tetrahydrofuran (50 ml) and added dropwise to a suspension of sodium borohydride (1.58 g, 41.91 mmol) in tetrahydrofuran (100 ml), which was cooled to 7° C. A solution of iodine (4.42 g, 17.46 mmol) in tetrahydrofuran was added dropwise, while the temperature was kept at 7° C. After the addition was finished, the reaction mixture was warmed to reflux for 16 h. The reaction mixture was cooled to 7° C., and methanol (250 ml) was added dropwise. The solvent was removed in vacuo. The residue was dissolved in 20% aqueous sodium hydroxide solution (250 ml) and tert-butyl methyl ether (100 ml). The phases were separated. The aqueous phase was extracted with tert-butyl methyl ether (2×100 ml). The combined organic layers were dried over magnesium sulfate. The solvent was removed in vacuo. The crude product was purified by flash chromatography on silica (400 g), using dichloromethane/methanol/25% aqueous ammonia (100:10:1) as eluent to give 2.76 g of N-methyl-N-(3-phenylpropyl)amine. was kept at 7° C After the addition the reaction mixture was warmed to reflux for 16 h The reaction mixture was cooled to 7° C. The solvent was removed in vacuo The residue was dissolved in 20% aqueous sodium hydroxide solution (250 ml) The phases were separated The aqueous phase was extracted with tert-butyl methyl ether (2×100 ml) The combined organic layers were dried over magnesium sulfate The solvent was removed in vacuo The crude product was purified by flash chromatography on silica (400 g)

Conditions: temp:7.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: N-(3-Phenylpropyl)formamide (5.70 g, 34.9 mmol) was dissolved in tetrahydrofuran (50 ml) and added dropwise to a suspension of sodium borohydride (1.58 g, 41.91 mmol) in tetrahydrofuran (100 ml), which was cooled to 7° C. A solution of iodine (4.42 g, 17.46 mmol) in tetrahydrofuran was added dropwise, while the temperature was kept at 7° C. After the addition was finished, the reaction mixture was warmed to reflux for 16 h. The reaction mixture was cooled to 7° C., and methanol (250 ml) was added dropwise. The solvent was removed in vacuo. The residue was dissolved in 20% aqueous sodium hydroxide solution (250 ml) and tert-butyl methyl ether (100 ml). The phases were separated. The aqueous phase was extracted with tert-butyl methyl ether (2×100 ml). The combined organic layers were dried over magnesium sulfate. The solvent was removed in vacuo. The crude product was purified by flash chromatography on silica (400 g), using dichloromethane/methanol/25% aqueous ammonia (100:10:1) as eluent to give 2.76 g of N-methyl-N-(3-phenylpropyl)amine. was kept at 7° C After the addition the reaction mixture was warmed to reflux for 16 h The reaction mixture was cooled to 7° C. The solvent was removed in vacuo The residue was dissolved in 20% aqueous sodium hydroxide solution (250 ml) The phases were separated The aqueous phase was extracted with tert-butyl methyl ether (2×100 ml) The combined organic layers were dried over magnesium sulfate The solvent was removed in vacuo The crude product was purified by flash chromatography on silica (400 g)

Conditions: temp:0.00; pressure:0.00; stir: