N-methyl-2-piperazin-1-ylethanamine

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

実験手順: Ethyl carbonochloridate (8.14 mL, 85.14 mmol) was added dropwise to N-methyl-2-piperazin-1-ylethanamine (5.0 g, 38.7 mmol) and triethylamine (12.95 mL, 92.88 mmol) in THF (40 mL) at 0° C. over a period of 10 minutes under N2. The resulting mixture was allowed to warm to r.t. and stirred for 2 h. The resulting white suspension was filtered, and washed through with THF (2×20 mL). The filtrate was concentrated in vacuo and the resulting residue was dissolved in EtOAc (75 mL). This solution was washed with sat. Na2CO3 (50 mL). The aqueous wash solution was then extracted with EtOAc (50 mL). The combined organic solutions were dried (MgSO4) and concentrated in vacuo to give crude intermediate (10.55 g). This was dissolved in THF (60 mL) and cooled to 0° C. LiAlH4 (101 mL, 100.6 mmol, 1M in THF) was added dropwise under N2. The resulting mixture was stirred at reflux overnight, then cooled to 0° C. and treated successively (dropwise) with water (3.8 mL), 15% aq. NaOH (3.8 mL) and water (11.4 mL) with rapid stirring. Diatomaceous earth (Celite™) and MgSO4 were added and the mixture was filtered, washed with EtOAc and the filtrate was concentrated in vacuo to give a colourless oil (3.35 g). The filtercake was washed with EtOAc (100 mL), heated to 70° C. and then filtered. The filtrate was concentrated in vacuo to give a further batch (1.023 g) of the title compound. Total: 4.37 g, 72%; 1H NMR: (CDCl3) 2.28 (3H, s), 2.33-2.6 (13H, m), 2.67 (2H, t). The resulting white suspension was filtered washed through with THF (2×20 mL) The filtrate was concentrated in vacuo the resulting residue was dissolved in EtOAc (75 mL) This solution was washed with sat. Na2CO3 (50 mL) The aqueous wash solution was then extracted with EtOAc (50 mL) The combined organic solutions were dried (MgSO4) concentrated in vacuo to give crude intermediate (10.55 g) cooled to 0° C The resulting mixture was stirred at reflux overnight cooled to 0° C. the mixture was filtered washed with EtOAc the filtrate was concentrated in vacuo