tert-butyl 4-(2-chloroethyl)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: Tert-butyl 4-(2-chloroethyl)piperazine-1-carboxylate (3.13 g, 12.58 mmol) was dissolved in methanol (20 ml), to which 40% methylamine methanol solution (30 ml) was added, and the mixture was heated under reflux for 5 hours. The reaction mixture was concentrated under reduced pressure, and the residue was dissolved in methylene chloride. The mixture was washed with saturated sodium hydrogencarbonate aqueous solution. The organic layer was dried over magnesium sulfate, and then filtered, and the filtrate was concentrated under reduced pressure to afford tert-butyl 4-(2-methylaminoethyl)piperazine-1-carboxylate (3.0 g, yield 98%) as a pale yellow oil. was added the mixture was heated under reflux for 5 hours The reaction mixture was concentrated under reduced pressure the residue was dissolved in methylene chloride The mixture was washed with saturated sodium hydrogencarbonate aqueous solution The organic layer was dried over magnesium sulfate filtered the filtrate was concentrated under reduced pressure

反応条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Into a 50-mL sealed tube, was placed tert-butyl 4-(2-chloroethyl)piperazine-1-carboxylate (300 mg, 1.21 mmol, 1.00 equiv), methanamine (in ethanol) (10 mL), NaI (100 mg). The resulting solution was stirred for 12 h at 70° C. in an oil bath. The resulting mixture was concentrated under vacuum. The resulting solution was diluted with 3 mL of water. The pH value of the solution was adjusted to 7-8 with sodium bicarbonate (5%). The resulting solution was extracted with 2×5 mL of dichloromethane and the organic layers combined. The resulting mixture was washed with 1×3 mL of water and 1×3 mL of brine. The resulting mixture was concentrated under vacuum. This resulted in 180 mg (crude) of tert-butyl 4-(2-(methylamino)ethyl)piperazine-1-carboxylate as brown oil Into a 50-mL sealed tube The resulting mixture was concentrated under vacuum The resulting solution was diluted with 3 mL of water The resulting solution was extracted with 2×5 mL of dichloromethane The resulting mixture was washed with 1×3 mL of water and 1×3 mL of brine The resulting mixture was concentrated under vacuum This resulted in 180 mg (crude) of tert-butyl 4-(2-(methylamino)ethyl)piperazine-1-carboxylate as brown oil

反応条件: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Into a 50-mL round-bottom flask, was placed a solution of tert-butyl 4-(2-hydroxyethyl)piperazine-1-carboxylate (2.31 g, 10.03 mmol, 1.00 equiv) in dichloromethane (20 mL) and a solution of thionyl chloride (1.5 mL, 2.00 equiv) in dichloromethane (3 mL) was added dropwise under ice-bath. The resulting solution was stirred overnight at 25° C. The resulting mixture was concentrated under vacuum. The resulting solution was diluted with 10 mL of water. The resulting solution was extracted with 2×25 mL of ethyl acetate and the organic layers combined. The resulting mixture was washed with 2×15 mL of sodium bicarbonate aq. and 2×10 mL of brine. The mixture was dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1:5). This resulted in 1.16 g (46%) of tert-butyl 4-(2-chloroethyl)piperazine-1-carboxylate as a off-white solid Into a 50-mL round-bottom flask, was placed The resulting mixture was concentrated under vacuum The resulting solution was diluted with 10 mL of water The resulting solution was extracted with 2×25 mL of ethyl acetate The resulting mixture was washed with 2×15 mL of sodium bicarbonate aq. and 2×10 mL of brine The mixture was dried over anhydrous sodium sulfate concentrated under vacuum This resulted in 1.16 g (46%) of tert-butyl 4-(2-chloroethyl)piperazine-1-carboxylate as a off-white solid

反応条件: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Into a 50-mL round-bottom flask, was placed a solution of tert-butyl 4-(2-hydroxyethyl)piperazine-1-carboxylate (2.31 g, 10.03 mmol, 1.00 equiv) in dichloromethane (20 mL) and a solution of thionyl chloride (1.5 mL, 2.00 equiv) in dichloromethane (3 mL) was added dropwise under ice-bath. The resulting solution was stirred overnight at 25° C. The resulting mixture was concentrated under vacuum. The resulting solution was diluted with 10 mL of water. The resulting solution was extracted with 2×25 mL of ethyl acetate and the organic layers combined. The resulting mixture was washed with 2×15 mL of sodium bicarbonate aq. and 2×10 mL of brine. The mixture was dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1:5). This resulted in 1.16 g (46%) of tert-butyl 4-(2-chloroethyl)piperazine-1-carboxylate as a off-white solid Into a 50-mL round-bottom flask, was placed The resulting mixture was concentrated under vacuum The resulting solution was diluted with 10 mL of water The resulting solution was extracted with 2×25 mL of ethyl acetate The resulting mixture was washed with 2×15 mL of sodium bicarbonate aq. and 2×10 mL of brine The mixture was dried over anhydrous sodium sulfate concentrated under vacuum This resulted in 1.16 g (46%) of tert-butyl 4-(2-chloroethyl)piperazine-1-carboxylate as a off-white solid

反応条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Into a 50-mL sealed tube, was placed tert-butyl 4-(2-chloroethyl)piperazine-1-carboxylate (300 mg, 1.21 mmol, 1.00 equiv), methylamine (in ethanol) (10 mL), and NaI (100 mg). The resulting solution was stirred for 12 h at 70° C. in an oil bath. The resulting mixture was concentrated under vacuum. The resulting solution was diluted with 3 mL of water and adjusted to pH 7-8 with sodium bicarbonate (5%). The resulting solution was extracted with 2×5 mL of dichloromethane and the organic layers combined. The resulting mixture was washed with 1×3 mL of water and 1×3 mL of brine. The resulting mixture was concentrated under vacuum. This resulted in 180 mg (crude) of tert-butyl 4-(2-(methylamino)ethyl)piperazine-1-carboxylate as brown oil. Into a 50-mL sealed tube The resulting mixture was concentrated under vacuum The resulting solution was diluted with 3 mL of water The resulting solution was extracted with 2×5 mL of dichloromethane The resulting mixture was washed with 1×3 mL of water and 1×3 mL of brine The resulting mixture was concentrated under vacuum This resulted in 180 mg (crude) of tert-butyl 4-(2-(methylamino)ethyl)piperazine-1-carboxylate as brown oil

反応条件: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Into a 50-mL round-bottom flask, was placed a solution of tert-butyl 4-(2-hydroxyethyl)piperazine-1-carboxylate (2.31 g, 10.03 mmol, 1.00 equiv) in dichloromethane (20 mL) and a solution of thionyl chloride (1.5 mL, 2.00 equiv) in dichloromethane (3 mL) was added dropwise at 0° C. The resulting solution was stirred overnight at 25° C. The resulting mixture was concentrated under vacuum. The resulting solution was diluted with 10 mL of water. The resulting solution was extracted with 2×25 mL of ethyl acetate and the organic layers combined. The resulting mixture was washed with 2×15 mL of sodium bicarbonate aq. and 2×10 mL of brine. The mixture was dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was applied onto a silica gel column and eluted with ethyl acetate/petroleum ether (1:5). This resulted in 1.16 g (46%) of tert-butyl 4-(2-chloroethyl)piperazine-1-carboxylate as a off-white solid. Into a 50-mL round-bottom flask, was placed The resulting mixture was concentrated under vacuum The resulting solution was diluted with 10 mL of water The resulting solution was extracted with 2×25 mL of ethyl acetate The resulting mixture was washed with 2×15 mL of sodium bicarbonate aq. and 2×10 mL of brine The mixture was dried over anhydrous sodium sulfate concentrated under vacuum eluted with ethyl acetate/petroleum ether (1:5) This resulted in 1.16 g (46%) of tert-butyl 4-(2-chloroethyl)piperazine-1-carboxylate as a off-white solid

反応条件: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Into a 50-mL round-bottom flask, was placed a solution of tert-butyl 4-(2-hydroxyethyl)piperazine-1-carboxylate (2.31 g, 10.03 mmol, 1.00 equiv) in dichloromethane (20 mL) and a solution of thionyl chloride (1.5 mL, 2.00 equiv) in dichloromethane (3 mL) was added dropwise at 0° C. The resulting solution was stirred overnight at 25° C. The resulting mixture was concentrated under vacuum. The resulting solution was diluted with 10 mL of water. The resulting solution was extracted with 2×25 mL of ethyl acetate and the organic layers combined. The resulting mixture was washed with 2×15 mL of sodium bicarbonate aq. and 2×10 mL of brine. The mixture was dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was applied onto a silica gel column and eluted with ethyl acetate/petroleum ether (1:5). This resulted in 1.16 g (46%) of tert-butyl 4-(2-chloroethyl)piperazine-1-carboxylate as a off-white solid. Into a 50-mL round-bottom flask, was placed The resulting mixture was concentrated under vacuum The resulting solution was diluted with 10 mL of water The resulting solution was extracted with 2×25 mL of ethyl acetate The resulting mixture was washed with 2×15 mL of sodium bicarbonate aq. and 2×10 mL of brine The mixture was dried over anhydrous sodium sulfate concentrated under vacuum eluted with ethyl acetate/petroleum ether (1:5) This resulted in 1.16 g (46%) of tert-butyl 4-(2-chloroethyl)piperazine-1-carboxylate as a off-white solid

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:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Into a 50-mL sealed tube, was placed tert-butyl 4-(2-chloroethyl)piperazine-1-carboxylate (300 mg, 1.21 mmol, 1.00 equiv), methanamine (in ethanol) (10 mL), NaI (100 mg). The resulting solution was stirred for 12 h at 70° C. in an oil bath. The resulting mixture was concentrated under vacuum. The resulting solution was diluted with 3 mL of water. The pH value of the solution was adjusted to 7-8 with sodium bicarbonate (5%). The resulting solution was extracted with 2×5 mL of dichloromethane and the organic layers combined. The resulting mixture was washed with 1×3 mL of water and 1×3 mL of brine. The resulting mixture was concentrated under vacuum. This resulted in 180 mg (crude) of tert-butyl 4-(2-(methylamino)ethyl)piperazine-1-carboxylate as brown oil Into a 50-mL sealed tube The resulting mixture was concentrated under vacuum The resulting solution was diluted with 3 mL of water The resulting solution was extracted with 2×5 mL of dichloromethane The resulting mixture was washed with 1×3 mL of water and 1×3 mL of brine The resulting mixture was concentrated under vacuum This resulted in 180 mg (crude) of tert-butyl 4-(2-(methylamino)ethyl)piperazine-1-carboxylate as brown oil