1-(2-bromophenyl)piperazine

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

Procedure: To a solution of 1-(2-bromophenyl)piperazine (3.0 g, 12.4 mmol) in tetrahydrofuran (30 mL) were added acetic acid (0.71 mL, 12.4 mmol), cyclopropanecarbaldehyde (1.39 mL, 18.66 mmol) and sodium triacetoxyborohydride (4.22 g, 19.9 mmol), followed by stirring for 88 hours at room temperature. Aqueous solution of potassium carbonate was added to the reaction mixture, extraction was performed with ethyl acetate, and the organic layer was concentrated. The resultant residue was purified by NH silica gel column chromatography (ethyl acetate/heptane) to give 3.773 g of the title compound as a colorless oil. the organic layer was concentrated The resultant residue was purified by NH silica gel column chromatography (ethyl acetate/heptane)

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

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

Procedure: In the manner given in Example 1A, p-nitrobenzenesulfonyl chloride, 1-(o-bromophenyl)piperazine and triethylamine are stirred at reflux to give 1-[(p-nitrophenyl)sulfonyl]-4-(o-bromophenyl)piperazine. at reflux

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

Procedure: In the manner given in Example 1A, p-nitrobenzenesulfonyl chloride, 1-(o-bromophenyl)piperazine and triethylamine are stirred at reflux to give 1-[(p-nitrophenyl)sulfonyl]-4-(o-bromophenyl)piperazine. at reflux

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

Procedure: To a solution of 1-(2-bromophenyl)piperazine (3.0 g, 12.4 mmol) in tetrahydrofuran (30 mL) were added acetic acid (0.71 mL, 12.4 mmol), cyclopropanecarbaldehyde (1.39 mL, 18.66 mmol) and sodium triacetoxyborohydride (4.22 g, 19.9 mmol), followed by stirring for 88 hours at room temperature. Aqueous solution of potassium carbonate was added to the reaction mixture, extraction was performed with ethyl acetate, and the organic layer was concentrated. The resultant residue was purified by NH silica gel column chromatography (ethyl acetate/heptane) to give 3.773 g of the title compound as a colorless oil. the organic layer was concentrated The resultant residue was purified by NH silica gel column chromatography (ethyl acetate/heptane)

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

Procedure: To a solution of 1-(2-bromophenyl)piperazine (3.0 g, 12.4 mmol) in tetrahydrofuran (30 mL) were added acetic acid (0.71 mL, 12.4 mmol), cyclopropanecarbaldehyde (1.39 mL, 18.66 mmol) and sodium triacetoxyborohydride (4.22 g, 19.9 mmol), followed by stirring for 88 hours at room temperature. Aqueous solution of potassium carbonate was added to the reaction mixture, extraction was performed with ethyl acetate, and the organic layer was concentrated. The resultant residue was purified by NH silica gel column chromatography (ethyl acetate/heptane) to give 3.773 g of the title compound as a colorless oil. the organic layer was concentrated The resultant residue was purified by NH silica gel column chromatography (ethyl acetate/heptane)

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

Procedure: To a solution of 1-(2-bromophenyl)piperazine (3.0 g, 12.4 mmol) in tetrahydrofuran (30 mL) were added acetic acid (0.71 mL, 12.4 mmol), cyclopropanecarbaldehyde (1.39 mL, 18.66 mmol) and sodium triacetoxyborohydride (4.22 g, 19.9 mmol), followed by stirring for 88 hours at room temperature. Aqueous solution of potassium carbonate was added to the reaction mixture, extraction was performed with ethyl acetate, and the organic layer was concentrated. The resultant residue was purified by NH silica gel column chromatography (ethyl acetate/heptane) to give 3.773 g of the title compound as a colorless oil. the organic layer was concentrated The resultant residue was purified by NH silica gel column chromatography (ethyl acetate/heptane)

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

Procedure: To a solution of 1-(2-bromophenyl)piperazine (3.0 g, 12.4 mmol) in tetrahydrofuran (30 mL) were added acetic acid (0.71 mL, 12.4 mmol), cyclopropanecarbaldehyde (1.39 mL, 18.66 mmol) and sodium triacetoxyborohydride (4.22 g, 19.9 mmol), followed by stirring for 88 hours at room temperature. Aqueous solution of potassium carbonate was added to the reaction mixture, extraction was performed with ethyl acetate, and the organic layer was concentrated. The resultant residue was purified by NH silica gel column chromatography (ethyl acetate/heptane) to give 3.773 g of the title compound as a colorless oil. the organic layer was concentrated The resultant residue was purified by NH silica gel column chromatography (ethyl acetate/heptane)

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

Procedure: Phenyl-N-(5-ethyl-2-methoxy-6-methylpyridin-3-yl)carbamate and 1-(2-bromophenyl)piperazine were reacted by the same way with the example 1 to obtain the titled compound.

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

Procedure: 1-(2-Bromophenyl)piperazine (200 mg) was dissolved in formaldehyde (36.5% in water, 0.603 mL) and the solution was stirred 3 h at RT. NaBH3CN (78.2 mg) was added and the mixture was stirred at RT overnight. NaBH3CN (78.2 mg) was added again and the mixture was stirred at RT for 6 h. The solvents were removed in vacuo and the residue was taken up in EA, washed with sat. NaHCO3, dried (Na2SO4) and evaporated to dryness. The residue was purified by CC (Biotage, SNAP 25 g cartridge, solvent A: Hept; solvent B: EA; gradient in % B: 18 for 4CV, 18 to 100 over 10CV, 100 for 2CV, then MeOH flush for 4CV) to afford 1-(2-bromophenyl)-4-methylpiperazine (111 mg, colorless oil). LC-MS (B): tR=0.57 min; [M+H]+: 255.05. the mixture was stirred at RT overnight the mixture was stirred at RT for 6 h The solvents were removed in vacuo washed with sat. NaHCO3 dried (Na2SO4) evaporated to dryness The residue was purified by CC (Biotage, SNAP 25 g cartridge, solvent A gradient in % B: 18 for 4CV, 18 to 100 over 10CV, 100 for 2CV, then MeOH flush for 4CV)

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

Procedure: In the manner given in Example 1A, p-nitrobenzenesulfonyl chloride, 1-(o-bromophenyl)piperazine and triethylamine are stirred at reflux to give 1-[(p-nitrophenyl)sulfonyl]-4-(o-bromophenyl)piperazine. at reflux