N-methyl-2-piperidin-1-ylethanamine

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: A solution of the title compound of Step 11 (1.85 g, 7.96mmol) and 20% Pd(OH)2 on carbon in EtOH (50 mL) was placed under a hydrogen atmosphere (60 psi) at room temperature for 17 hours. The mixture was filtered and concentrated to give the title compound as a clear, yellow liquid (1.02 g, 90% crude yield). The proton spectral data were consistent with the proposed structure. at room temperature for 17 hours The mixture was filtered concentrated

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

Procedure: A solution of the title compound of Step 11 (1.85 g, 7.96mmol) and 20% Pd(OH)2 on carbon in EtOH (50 mL) was placed under a hydrogen atmosphere (60 psi) at room temperature for 17 hours. The mixture was filtered and concentrated to give the title compound as a clear, yellow liquid (1.02 g, 90% crude yield). The proton spectral data were consistent with the proposed structure. at room temperature for 17 hours The mixture was filtered concentrated

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

Procedure: To a solution of 4-bromophenylacetic acid (10 g, 46.5 mmol) in CHCl3 (100ml) was added thionyl chloride (8 ml) in CHCl3 (10 ml) and three drops of DMF. The mixture was reflux for one to two hours. The volatiles were removed in vacuo to give a light yellow oil. This acid chloride was dissolved in CHCl330ml and added dropwise to another flask containing N-methyl-2-(1-piperidinyl)ethyl amine (6.1 g, 48 mmol) and triethylamine (25 ml) and CHCl3 (100ml) at 0° C. The reaction mixture was stirred overnight at room. The volatiles were removed, the residue dissolved in CHCl3 (150 ml) and washed with (2×100 ml) water and 2% NaHCO3 (50 ml). The organic layer was dried and the volatiles were removed to give a light yellow oil (15.0 g). The oil was passed through a silica gel column and eluted with CHCl3/MeOH to give 13 g, (87%) of the desired pure compound. 1H NMR 1.30-1.54, (m, 6H, piperidinyl CH2); 2.33-2.43 (m, 6H, NCH2); 2.92 (44%), 2.96 (56%) (s, 3H, N-Me); 3.32-3.37 (46%), 3.45-3.49 (54%), (t, 2H, J=7.1Hz., NCH2); 3.61 (56%), 3.67 (44%), (s, 2H, benzylic); 7.09-7.11 (d, 2H, arom); 7.38-7.41 (d, 2H, arom). The mixture was reflux for one to two hours The volatiles were removed in vacuo to give a light yellow oil added dropwise to another flask The volatiles were removed the residue dissolved in CHCl3 (150 ml) washed with (2×100 ml) water and 2% NaHCO3 (50 ml) The organic layer was dried the volatiles were removed

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

Procedure: To a solution of 4-bromophenylacetic acid (10 g, 46.5 mmol) in CHCl3 (100 ml) was added thionyl chloride (8 ml) in CHCl3 (10 ml) and three drops of DMF. The mixture was reflux for one to two hours. The volatiles were removed in vacuo to give a light yellow oil. This acid chloride was dissolved in CHCl3 30 ml and added dropwise to another flask containing N-methyl-2-(1-piperidinyl)ethyl amine (6.1 g, 48 mmol) and triethylamine (25 ml) and CHCl3 (100 ml) at 0° C. The reaction mixture was stirred overnight at room. The volatiles were removed, the residue dissolved in CHCl3 (150 ml) and washed with (2×100 ml) water and 2% NaHCO3 (50 ml). The organic layer was dried and the volatiles were removed to give a light yellow oil (15.0 g). The oil was passed through a silica gel column and eluted with CHCl3 /MeOH to give 13 g, (87%) of the desired pure compound. 1H NMR 1.30-1.54 (m, 6H, piperidinyl CH2); 2.33-2.43 (m, 6H, NCH2); 2.92 (44%), 2.96 (56%) (s, 3H, N-Me); 3.32-3.37 (46%), 3.45-3.49 (54%), (t, 2H, J=7.1 Hz, NCH2); 3.61 (56%), 3.67 (44%), (s, 2H, benzylic); 7.09-7.11 (d, 2H, arom); 7.38-7.41 (d, 2H, arom). The mixture was reflux for one to two hours The volatiles were removed in vacuo to give a light yellow oil added dropwise to another flask The volatiles were removed the residue dissolved in CHCl3 (150 ml) washed with (2×100 ml) water and 2% NaHCO3 (50 ml) The organic layer was dried the volatiles were removed

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

Procedure: A solution of the title compound of Step 11 (1.85 g, 7.96mmol) and 20% Pd(OH)2 on carbon in EtOH (50 mL) was placed under a hydrogen atmosphere (60 psi) at room temperature for 17 hours. The mixture was filtered and concentrated to give the title compound as a clear, yellow liquid (1.02 g, 90% crude yield). The proton spectral data were consistent with the proposed structure. at room temperature for 17 hours The mixture was filtered concentrated

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

Procedure: A solution of 8.0 g of N-(2-chloroethyl)piperidine hydrochloride and 0.5 g of sodium iodide in 60 ml of methanol which contained 40% of methylamine was reacted at 70° C. in a sealed tube for 20 hours. After allowing the reaction mixture to cool down, the reaction mixture was concentrated under reduced pressure. The residue was added with ether, followed by a further addition of 10 g of ground sodium hydroxide. The resulting mixture was stirred for 2 hours. The insoluble material was filtered off and the filtrate was concentrated under the atmospheric pressure. The residue was distilled under reduced pressure to give 4.5 g of a fraction at 80° C./18 Torr (yield: 73%). was reacted at 70° C. in a sealed tube for 20 hours to cool down the reaction mixture was concentrated under reduced pressure The residue was added with ether followed by a further addition of 10 g of ground sodium hydroxide The insoluble material was filtered off the filtrate was concentrated under the atmospheric pressure The residue was distilled under reduced pressure to give 4.5 g of a fraction at 80° C./18 Torr (yield: 73%)

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

Procedure: A solution of 8.0 g of N-(2-chloroethyl)piperidine hydrochloride and 0.5 g of sodium iodide in 60 ml of methanol which contained 40% of methylamine was reacted at 70° C. in a sealed tube for 20 hours. After allowing the reaction mixture to cool down, the reaction mixture was concentrated under reduced pressure. The residue was added with ether, followed by a further addition of 10 g of ground sodium hydroxide. The resulting mixture was stirred for 2 hours. The insoluble material was filtered off and the filtrate was concentrated under the atmospheric pressure. The residue was distilled under reduced pressure to give 4.5 g of a fraction at 80° C./18 Torr (yield: 73%). was reacted at 70° C. in a sealed tube for 20 hours to cool down the reaction mixture was concentrated under reduced pressure The residue was added with ether followed by a further addition of 10 g of ground sodium hydroxide The insoluble material was filtered off the filtrate was concentrated under the atmospheric pressure The residue was distilled under reduced pressure to give 4.5 g of a fraction at 80° C./18 Torr (yield: 73%)

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

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

Procedure: A solution of 8.0 g of N-(2-chloroethyl)piperidine hydrochloride and 0.5 g of sodium iodide in 60 ml of methanol which contained 40% of methylamine was reacted at 70° C. in a sealed tube for 20 hours. After allowing the reaction mixture to cool down, the reaction mixture was concentrated under reduced pressure. The residue was added with ether, followed by a further addition of 10 g of ground sodium hydroxide. The resulting mixture was stirred for 2 hours. The insoluble material was filtered off and the filtrate was concentrated under the atmospheric pressure. The residue was distilled under reduced pressure to give 4.5 g of a fraction at 80° C./18 Torr (yield: 73%). was reacted at 70° C. in a sealed tube for 20 hours to cool down the reaction mixture was concentrated under reduced pressure The residue was added with ether followed by a further addition of 10 g of ground sodium hydroxide The insoluble material was filtered off the filtrate was concentrated under the atmospheric pressure The residue was distilled under reduced pressure to give 4.5 g of a fraction at 80° C./18 Torr (yield: 73%)

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

Procedure: By using piperidine (983.5 mg) as a starting material, the title compound (120 mg) was obtained in the same manners as those of Reference Example 1, (1) and Reference Example 19, (3).