反应详情

Under a nitrogen atmosphere a mixture of 3.11 g (12.0 mmol) 1-benzyl-4-piperidin-4-yl-piperazine and 7.50 mL (12.0 mmol, 15% in water) 4-oxo-butyric acid in 70 mL THF was adjusted to a pH of 5 with AcOH and stirred for 1 h at RT. After cooling to 0° C., 5.35 g (24.0 mmol) sodium triacetoxyborohydride were added batchwise and the reaction mixture was stirred overnight at RT. Within 15 min 80 mL of 30% K2CO3 solution were added dropwise, the aqueous phase was washed twice with EtOAc and evaporated down by half i. vac. 1 M KHSO4 solution was added, the precipitate formed was removed by suction filtering, the filtrate was washed with EtOAc and the aqueous phase was evaporated to dryness i. vac. The residue was taken up in 150 mL ethanolic HCl (1.25 M) and the reaction mixture was stirred overnight at RT. It was evaporated down i. vac., the residue was taken up in a little 15% K2CO3 solution, extracted exhaustively with EtOAc and the combined organic phases were dried over Na2SO4. After elimination of the desiccant and solvent the residue was further reacted without any further purification.

1. temperatureAfter cooling to 0° C.
2. stirringthe reaction mixture was stirred overnight at RT
3. washthe aqueous phase was washed twice with EtOAc
4. customevaporated down by half i
5. addition1 M KHSO4 solution was added
6. customthe precipitate formed
7. customwas removed by suction
8. filtrationfiltering
9. washthe filtrate was washed with EtOAc
10. customthe aqueous phase was evaporated to dryness i
11. stirringthe reaction mixture was stirred overnight at RT
12. customIt was evaporated down i
13. extractionextracted exhaustively with EtOAc
14. dry with materialthe combined organic phases were dried over Na2SO4
15. customAfter elimination of the desiccant and solvent the residue was further reacted without any further purification