反应详情

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).

1. filtrationThe resulting white suspension was filtered
2. washwashed through with THF (2×20 mL)
3. concentrationThe filtrate was concentrated in vacuo
4. dissolutionthe resulting residue was dissolved in EtOAc (75 mL)
5. washThis solution was washed with sat. Na2CO3 (50 mL)
6. extractionThe aqueous wash solution was then extracted with EtOAc (50 mL)
7. dry with materialThe combined organic solutions were dried (MgSO4)
8. concentrationconcentrated in vacuo
9. customto give crude intermediate (10.55 g)
10. temperaturecooled to 0° C
11. stirringThe resulting mixture was stirred
12. temperatureat reflux overnight
13. temperaturecooled to 0° C.
14. filtrationthe mixture was filtered
15. washwashed with EtOAc
16. concentrationthe filtrate was concentrated in vacuo