ethyl 1-benzylpiperazine-2-carboxylate

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

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

Procedure: Ethyl 1-benzylpiperazine-2-carboxylate (3.03 g, 12.2 mmol) was reacted with iodomethane (1.73 g, 12.2 mmol) according to the procedure as described in Example 48, Step A to give the title compound as yellow oil (2.33 g, 73%). The compound was characterized by the following spectroscopic data:

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

Procedure: To a solution of ethyl 1,4-dibenzylpiperazine-2-carboxylate (6.76 g, 20 mmol) in 1,2-dichloroethane (20 mL) was added 1-chloroethyl carbonochloridate (3.15 g, 22 mmol) dropwise over a period of 30 minutes at 0° C., and the mixture was stirred at the temperature for another 15 minutes. Then the mixture was stirred at 90° C. for 1 hour. The mixture was concentrated in vacuo, and to the residue was added methanol (15 mL). The mixture was stirred at 70° C. for 1 hour and concentrated in vacuo. The residue was diluted with water and washed with DCM. The aqueous layer was adjusted to pH 9 with NaHCO3 aqueous solution and extracted with DCM. The organic layer was dried over Na2SO4, and concentrated in vacuo to give the title compound as yellow oil (3.06 g, 60%). The compound was characterized by the following spectroscopic data: Then the mixture was stirred at 90° C. for 1 hour The mixture was concentrated in vacuo to the residue was added methanol (15 mL) The mixture was stirred at 70° C. for 1 hour concentrated in vacuo The residue was diluted with water washed with DCM extracted with DCM The organic layer was dried over Na2SO4 concentrated in vacuo

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

Procedure: To a solution of ethyl 1,4-dibenzylpiperazine-2-carboxylate (6.76 g, 20 mmol) in 1,2-dichloroethane (20 mL) was added 1-chloroethyl carbonochloridate (3.15 g, 22 mmol) dropwise over a period of 30 minutes at 0° C., and the mixture was stirred at the temperature for another 15 minutes. Then the mixture was stirred at 90° C. for 1 hour. The mixture was concentrated in vacuo, and to the residue was added methanol (15 mL). The mixture was stirred at 70° C. for 1 hour and concentrated in vacuo. The residue was diluted with water and washed with DCM. The aqueous layer was adjusted to pH 9 with NaHCO3 aqueous solution and extracted with DCM. The organic layer was dried over Na2SO4, and concentrated in vacuo to give the title compound as yellow oil (3.06 g, 60%). The compound was characterized by the following spectroscopic data: Then the mixture was stirred at 90° C. for 1 hour The mixture was concentrated in vacuo to the residue was added methanol (15 mL) The mixture was stirred at 70° C. for 1 hour concentrated in vacuo The residue was diluted with water washed with DCM extracted with DCM The organic layer was dried over Na2SO4 concentrated in vacuo

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

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

Procedure: Using an analogous procedure to that described in Example 1, 1-(4-pyridyl)piperidine-4-carbonyl chloride was reacted with ethyl 1-benzylpiperazine-2-carboxylate (Helv. Chim. Acta, 1962, 45, 2383) to give 1-benzyl-2-ethoxycarbonyl-4-[1-(4-pyridyl)piperidin-4-ylcarbonyl]piperazine in 67% yield.

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

Procedure: Using an analogous procedure to that described in Example 1, 1-(4-pyridyl)piperidine-4-carbonyl chloride was reacted with ethyl 1-benzylpiperazine-2-carboxylate (Helv. Chim. Acta, 1962, 45, 2383) to give 1-benzyl-2-ethoxycarbonyl-4-[1-(4-pyridyl)piperidin-4-ylcarbonyl]piperazine in 67% yield.

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

Procedure: Using an analogous procedure to that described in Example 1, 1-(4-pyridyl)piperidine-4-carbonyl chloride was reacted with ethyl 1-benzylpiperazine-2-carboxylate (Helv. Chim. Acta, 1962, 45, 2383) to give 1-benzyl-2-ethoxycarbonyl-4-[1-(4-pyridyl)piperidin-4-ylcarbonyl]piperazine in 67% yield.

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

Procedure: A solution of 1-benzyl-piperazine-2-carboxylic acid ethyl ester (300 mg) in DMF (13 mL) was treated with triethylamine (0.5 mL) and 3-methoxybenzene sulfonyl chloride (274.6 mg) at RT for 2 hours. Water was added, and the inorganic layer was extracted with ethyl acetate (×3). The combined organic layers were dried (Na2SO4), filtered and evaporated to yield 1-benzyl-4-(3-methoxy-benzenesulfonyl)-piperazine-2-carboxylic acid ethyl ester as a colorless oil (417 mg), MS: 419.3 ([M+H]+). the inorganic layer was extracted with ethyl acetate (×3) The combined organic layers were dried (Na2SO4) filtered evaporated

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

Procedure: Under argon at 0° C., to a solution of ethyl 1,4-dibenzylpiperazine-2-carboxylate (10 g) in dichloroethane (40 mL) a solution of 1-chloroethyl chloroformate (4.73 mL) in dichloroethane (14 mL) was added dropwise over a period of 10 min. The reaction mixture was stirred for 15 minutes at 0° C., and then heated to reflux overnight. The solvent was evaporated and the crude material was dissolved in ethanol and heated at reflux overnight. The solvent was evaporated and the residue was dissolved in water and extracted with diethyl ether (×2) and CH2Cl2 (×2). A saturated solution of NaHCO3 was then added to the water phase, and the inorganic phase was extracted with CH2Cl2 (×2). The organic layers were then combined, washed with brine, dried (Na2SO4), filtered and concentrated to give 1-benzyl-piperazine-2-carboxylic acid ethyl ester as crude product, MS: 248.9 ([M+H]+). heated to reflux overnight The solvent was evaporated the crude material was dissolved in ethanol heated at reflux overnight The solvent was evaporated the residue was dissolved in water extracted with diethyl ether (×2) and CH2Cl2 (×2) A saturated solution of NaHCO3 was then added to the water phase the inorganic phase was extracted with CH2Cl2 (×2) washed with brine dried (Na2SO4) filtered concentrated

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

Procedure: Using an analogous procedure to that described in Example 2, ethyl 1-benzylpiperazine-2-carboxylate was reacted with 2-naphthylsulphonyl chloride to give ethyl 1-benzyl-4-(2-naphthylsulphonyl)piperazine-2-carboxylate in 93% yield.

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

Procedure: Using an analogous procedure to that described in Example 1, 1-(4-pyridyl)piperidine-4-carbonyl chloride was reacted with ethyl 1-benzylpiperazine-2-carboxylate (Helv. Chim. Acta, 1962, 45, 2383) to give 1-benzyl-2-ethoxycarbonyl-4-[1-(4-pyridyl)piperidin-4-ylcarbonyl]-piperazine in 67% yield.