tert-butyl 4-(oxiran-2-ylmethyl)piperazine-1-carboxylate

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of tert-butyl piperazine-1-carboxylate (6.2 g, 33.29 mmol), epibromohydrin (5.4 g, 39.42 mmol) and potassium carbonate (5.5 g, 39.79 mmol) in acetonitrile (70 ml) was heated under reflux for 3 hours. The reaction mixture was concentrated under reduced pressure, and water was added to the residue. The mixture was extracted with methylene chloride. The extract was washed with brine, dried over sodium sulfate, and then filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate) to afford tert-butyl 4-oxiranylmethylpiperazine-1-carboxylate (6.2 g, yield 77%) as a colorless oil. was heated under reflux for 3 hours The reaction mixture was concentrated under reduced pressure, and water was added to the residue The mixture was extracted with methylene chloride The extract was washed with brine dried over sodium sulfate filtered the filtrate was concentrated under reduced pressure The residue was purified by silica gel column chromatography (ethyl acetate)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The same method as employed in the preparation of Example 1 but starting from 3,6-dichloro-9H-carbazole and (±)-4-oxiranylmethyl-piperazine-1-carboxylic acid tert-butyl ester gives after flash chromatography the title compound as a white foam in a 74% yield. The same method as employed in the preparation of Example 1

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The same method as employed in the preparation of Example 1 but starting from 3,6-dibromo-9H-carbazole, (±)-4-oxiranylmethyl-piperazine-1-carboxylic acid tert-butyl ester and sodium hydride gives after flash chromatography the title compound as a white foam in a 72% yield. M.p: 90-95° C. The same method as employed in the preparation of Example 1

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The same method as employed in the preparation of Example 1 but starting from 3,6-dibromo-9H-carbazole, (±)-4-oxiranylmethyl-piperazine-1-carboxylic acid tert-butyl ester and sodium hydride gives after flash chromatography the title compound as a white foam in a 72% yield. M.p: 90-95° C. The same method as employed in the preparation of Example 1

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The same method as employed in the preparation of Example 1 but starting from 9H-carbazole and (±)-4-oxiranylmethyl-piperazine-1-carboxylic acid tert-butyl ester (prepared according to the procedure of Toldy, L. et al., WO 97/14685) gives after flash chromatography the title compound as a pale yellow foam in a 82% yield. The same method as employed in the preparation of Example 1 prepared

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The same method as employed in the preparation of Example 1 but starting from 9H-carbazole and (±)-4-oxiranylmethyl-piperazine-1-carboxylic acid tert-butyl ester (prepared according to the procedure of Toldy, L. et al., WO 97/14685) gives after flash chromatography the title compound as a pale yellow foam in a 82% yield. The same method as employed in the preparation of Example 1 prepared

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 1-(tert-butoxycarbonyl)piperazine (18.6 g, 100 mmol) and epichlorohydrine (10.2 ml, 12.0 g, 130 mmol) in methanol (50 ml) was stirred at room temperature for 24 hours and the solvent was evaporated. The residue was dissolved in 200 ml of ether and the solution was stirred with 10N aqueous NaOH (100 ml) at room temperature for 2 hours. Then the organic layer was separated, washed with brine until neutral, dried over MgSO4 and concentrated to afford the title compound (21.8 g) as a pale yellowish viscous oil, yield: 90.1%. the solvent was evaporated The residue was dissolved in 200 ml of ether Then the organic layer was separated washed with brine until neutral, dried over MgSO4 concentrated

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The same method as employed in the preparation of Example 1 but starting from 3,6-dichloro-9H-carbazole and (±)-4-oxiranylmethyl-piperazine-1-carboxylic acid tert-butyl ester gives after flash chromatography the title compound as a white foam in a 74% yield. The same method as employed in the preparation of Example 1