N-methyl-N-(2-phenylethyl)piperidin-4-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:; See reaction.notes.procedure_details.

Procedure: 1.0 ml of phenyl isocyanate was added to a solution of 1.0 g of 4-[N-methyl-N-(2-phenylethyl)-amino]piperidine in 15 ml of chloroform. The mixture was stirred at room temperature for 2 hours. The reaction mixture was concentrated under reduced pressure. To the residue was added diethyl ether for crystallization. The resulting crystals were collected by filtration and recrystallized from ethyl acetate to obtain 0.7 g of 4-[N-methyl-N-(2-phenylethyl)amino]-1-anilinocarbonylpiperidine as colorless prism-like crystals. The reaction mixture was concentrated under reduced pressure To the residue was added diethyl ether for crystallization The resulting crystals were collected by filtration recrystallized from ethyl acetate

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

Procedure: 60 ml of concentrated hydrochloric acid and 13.3 g of 10% palladium-carbon were added to a solution of 266 g of 4-[N-methyl-N-(2-phenylethyl)amino]-1-benzylpiperidine in 1 liter of ethanol and 500 ml of water. The mixture was stirred at a hydrogen pressure of 1 atm. at 60° C. for 5 hours. 10% palladium-carbon was removed by filtration and then washed with ethanol. The filtrate and the washings were combined and concentrated under reduced pressure. The residue was added to ice water. The mixture was made alkaline with a 25% aqueous sodium hydroxide solution and then extracted with methylene chloride. The extract was water-washed and then concentrated under reduced pressure. The residue was subjected to vacuum distillation to obtain 131.9 g of 4-[N-methyl-N-(2-phenylethyl)amino]piperidine as a colorless oil. 10% palladium-carbon was removed by filtration washed with ethanol concentrated under reduced pressure The residue was added to ice water extracted with methylene chloride washed concentrated under reduced pressure The residue was subjected to vacuum distillation

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

Procedure: 1.0 ml of phenyl isocyanate was added to a solution of 1.0 g of 4-[N-methyl-N-(2-phenylethyl)amino]piperidine in 15 ml of chloroform. The mixture was stirred at room temperature for 2 hours. The reaction mixture was concentrated under reduced pressure. To the residue was added diethyl ether for crystallization. The resulting crystals were collected by filtration and recrystallized from ethyl acetate to obtain 0.7 g of 4-[N-methyl-N-(2-phenylethyl)amino]-1-anilinocarbonylpiperidine as colorless prism-like crystals. The reaction mixture was concentrated under reduced pressure To the residue was added diethyl ether for crystallization The resulting crystals were collected by filtration recrystallized from ethyl acetate

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

Procedure: 60 ml of concentrated hydrochloric acid and 13.3 g of 10% palladium-carbon were added to a solution of 266 g of 4-[N-methyl-N-(2-phenylethyl)amino]-1-benzylpiperidine in 1 liter of ethanol and 500 ml of water. The mixture was stirred at a hydrogen pressure of 1 atm. at 60° C. for 5 hours. 10% palladium-carbon was removed by filtration and then washed with ethanol. The filtrate and the washings were combined and concentrated under reduced pressure. The residue was added to ice water. The mixture was made alkaline with a 25% aqueous sodium hydroxide solution and then extracted with methylene chloride. The extract was water-washed and then concentrated under reduced pressure. The residue was subjected to vacuum distillation to obtain 131.9 g of 4-[N-methyl-N-(2-phenylethyl)amino]piperidine as a colorless oil. 10% palladium-carbon was removed by filtration washed with ethanol concentrated under reduced pressure The residue was added to ice water extracted with methylene chloride washed concentrated under reduced pressure The residue was subjected to vacuum distillation

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

Procedure: A solution of the product of Example 9 (152 mg), methyl-phenethyl-piperidin -4-yl-amine (128 mg), and acetic acid (0.11 mL) in DCM (3 mL) was treated with sodium triacetoxyborohydride (190 mg). After 16 h, the resulting mixture was treated with 10% sodium hydroxide (5 mL) and extracted with DCM (3×10 mL). The combined organic phases were dried (sodium sulfate) and evaporated. Chromatography of the residue (1–5% 2 M methanolic ammonia/DCM) gave the title compound as a colorless oil (148 mg). 1H NMR (400 MHz, CDCl3): 7.29–7.25 (m, 2H), 7.21–7.16 (m, 5H), 6.83 (j, J=8.6 Hz, 2H), 3.99 (d, J=6.3 Hz, 2H), 3.41 (s, 2H); 2.92 (m, 2H), 2.77–2.66 (m, 4H), 2.47 (m, 2H), 2.40 (m, 4H), 2.34 (s, 3H), 2.00–1.88 (m, 4H), 1.71 (m, 2H), 1.62–1.55 (m, 6H), 1.44 (m, 2H). extracted with DCM (3×10 mL) The combined organic phases were dried (sodium sulfate) evaporated

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

Procedure: 1.0 ml of phenyl isocyanate was added to a solution of 1.0 g of 4-[N-methyl-N-(2-phenylethyl)-amino]piperidine in 15 ml of chloroform. The mixture was stirred at room temperature for 2 hours. The reaction mixture was concentrated under reduced pressure. To the residue was added diethyl ether for crystallization. The resulting crystals were collected by filtration and recrystallized from ethyl acetate to obtain 0.7 g of 4-[N-methyl-N-(2-phenylethyl)amino]-1-anilinocarbonylpiperidine as colorless prism-like crystals. The reaction mixture was concentrated under reduced pressure To the residue was added diethyl ether for crystallization The resulting crystals were collected by filtration recrystallized from ethyl acetate

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

Procedure: 60 ml of concentrated hydrochloric acid and 13.3 g of 10% palladium-carbon were added to a solution of 266 g of 4-[N-methyl-N-(2-phenylethyl)amino]-1-benzylpiperidine in 1 liter of ethanol and 500 ml of water. The mixture was stirred at a hydrogen pressure of 1 atm. at 60° C. for 5 hours. 10% palladium-carbon was removed by filtration and then washed with ethanol. The filtrate and the washings were combined and concentrated under reduced pressure. The residue was added to ice water. The mixture was made alkaline with a 25% aqueous sodium hydroxide solution and then extracted with methylene chloride. The extract was water-washed and then concentrated under reduced pressure. The residue was subjected to vacuum distillation to obtain 131.9 g of 4-[N-methyl-N-(2-phenylethyl)amino]piperidine as a colorless oil. 10% palladium-carbon was removed by filtration washed with ethanol concentrated under reduced pressure The residue was added to ice water extracted with methylene chloride washed concentrated under reduced pressure The residue was subjected to vacuum distillation

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

Procedure: 60 ml of concentrated hydrochloric acid and 13.3 g of 10% palladium-carbon were added to a solution of 266 g of 4-[N-methyl-N-(2-phenylethyl)amino]-1-benzylpiperidine in 1 liter of ethanol and 500 ml of water. The mixture was stirred at a hydrogen pressure of 1 atm. at 60° C. for 5 hours. 10% palladium-carbon was removed by filtration and then washed with ethanol. The filtrate and the washings were combined and concentrated under reduced pressure. The residue was added to ice water. The mixture was made alkaline with a 25% aqueous sodium hydroxide solution and then extracted with methylene chloride. The extract was water-washed and then concentrated under reduced pressure. The residue was subjected to vacuum distillation to obtain 131.9 g of 4-[N-methyl-N-(2-phenylethyl)amino]piperidine as a colorless oil. 10% palladium-carbon was removed by filtration washed with ethanol concentrated under reduced pressure The residue was added to ice water extracted with methylene chloride washed concentrated under reduced pressure The residue was subjected to vacuum distillation

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

Procedure: A solution of the product of Example 9 (152 mg), methyl-phenethyl-piperidin-4-yl-amine (128 mg), and acetic acid (0.11 mL) in DCM (3 mL) was treated with sodium triacetoxyborohydride (190 mg). After 16 h, the resulting mixture was treated with 10% sodium hydroxide (5 mL) and extracted with DCM (3×10 mL). The combined organic phases were dried (sodium sulfate) and evaporated. Chromatography of the residue (1-5% 2 M methanolic ammonia/DCM) gave the title compound as a colorless oil (148 mg). 1H NMR (400 MHz, CDCl3): 7.29-7.25 (m, 2H), 7.21-7.16 (m, 5H), 6.83 (j, J=8.6 Hz, 2H), 3.99 (d, J=6.3 Hz, 2H), 3.41 (s, 2H), 2.92 (m, 2H), 2.77-2.66 (m, 4H), 2.47 (m, 2H), 2.40 (m, 4H), 2.34 (s, 3H), 2.00-1.88 (m, 4H), 1.71 (m, 2H), 1.62-1.55 (m, 6H), 1.44 (m, 2H). extracted with DCM (3×10 mL) The combined organic phases were dried (sodium sulfate) evaporated

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