反应详情

温度

0 °C

(S)-2-[(Azepane-1-carbonyl)-amino]-propanoic acid (0.300 g, 1.40 mmol) was dissolved in dry DMF (4 mL) under nitrogen atmosphere and cooled to 0° C. in an ice-water bath. To this solution were added, in succession, N,N-diisopropylethylamine (0.732 mL, 4.20 mmol) and solid O-benzotriazol-1-yl-N,N,N′,N′-tetramethyluronium hexafluorophosphate (0.531 g, 1.40 mmol). The resulting reaction mixture was stirred at that temperature for 35 minutes; solid 4,4-bis-(4-fluoro-phenyl)-butylamine monohydrochloride (0.412 g, 1.40 mmol) was then added. After stirring for, sequentially, 10 minutes at 0° C. and 40 minutes at ambient temperature, reaction mixture was mixed with 60 mL of diethyl ether; the resulting mixture was successively washed with saturated aqueous NaHCO3 solution (2×60 mL), brine (2×60 mL), and was dried over Na2SO4. The solution was concentrated in vacuo affording an viscous oil. The crude product was further purified by flash chromatography (70% EtOAc in hexanes) to afford 0.42 g (65%) of the pure titled compound as a white foam: mp 29-49° C. APCI-MS m/z 458.3 (MH+).

1. customThe resulting reaction mixture
2. stirringAfter stirring for, sequentially, 10 minutes at 0° C.
3. custom40 minutes at ambient temperature, reaction mixture
4. washthe resulting mixture was successively washed with saturated aqueous NaHCO3 solution (2×60 mL), brine (2×60 mL)
5. dry with materialwas dried over Na2SO4
6. concentrationThe solution was concentrated in vacuo
7. customaffording an viscous oil
8. customThe crude product was further purified by flash chromatography (70% EtOAc in hexanes)