反应详情

A solution of 8.52 g (39.75 mmol) of 5-oxo-[1,4]diazepane-1-carboxylic acid tert-butyl ester in 200 ml of DMA was treated at 0° C. with 2.60 g (59.62 mmol) of NaH (55% dispersion in oil) in small portions. The reaction was stirred 1 h at this temperature, then the free 1-(3-chloropropyl)piperidine in 200 ml toluene was dropped in [49.62 g (250.42 mmol, 6.3 eq.) 1-(3-chloropropyl)piperidine hydrochloride were dissolved in 262 ml of 1 M aq. 1N NaOH solution and extracted with toluene (200 ml). The organic phase was dried over Na2SO4]. The reaction was warmed up to RT and stirred over night. After 2 h at 50° C. and cooling to RT, the reaction was neutralized with water (50 ml), evaporated and then dissolved in aq. sat. NaHCO3 solution/Et2O. After reextraction with Et2O, the organic phase was dried (Na2SO4), evaporated and crystallized from pentane to yield 12.08 g (90%) of the title compound as white crystals. MS: 340.2 (MH+).

1. extractionextracted with toluene (200 ml)
2. dry with materialThe organic phase was dried over Na2SO4]
3. stirringstirred over night
4. waitAfter 2 h at 50° C.
5. temperaturecooling to RT
6. customevaporated
7. dissolutiondissolved in aq. sat. NaHCO3 solution/Et2O
8. dry with materialAfter reextraction with Et2O, the organic phase was dried (Na2SO4)
9. customevaporated
10. customcrystallized from pentane