反应详情

温度

0 °C

(S)-2-[(Azepane-1-carbonyl)-amino]-3-methyl-butyric acid (0.26 g, 1.1 mmol, Example 26, Step B) was dissolved in dry DMF (5 mL) under nitrogen atmosphere and cooled to 0° C. in an ice-water bath. To this solution were added, in succession, N,N-diisopropylethylamine (0.37 mL, 2.1 mmol) and solid O-benzotriazol-1-yl-N,N,N′,N′-tetramethyluronium hexafluorophosphate (0.40 g, 1.1 mmol). The resulting reaction mixture was stirred at that temperature for 30 minutes; solid 1-bis(4-fluorophenyl)methyl piperazine (0.31 g, 1.1 mmol) was then added. After additional 90 minutes stirring at 0° C., reaction mixture was mixed with 60 mL of diethyl ether; the resulting mixture was successively washed with saturated aqueous NaHCO3 solution (2×50 mL), brine (2×50 mL), and dried over Na2SO4. The solution was concentrated in vacuo affording a viscous oil. The crude product was further purified by flash chromatography (60% EtOAc in hexane) to provide 0.45 g (82%) of the pure titled compound as a white foam; mp 72-82° C. APCI-MS m/z 513.2 (MH+).

1. customThe resulting reaction mixture
2. stirringAfter additional 90 minutes stirring at 0° C.
3. customreaction mixture
4. washthe resulting mixture was successively washed with saturated aqueous NaHCO3 solution (2×50 mL), brine (2×50 mL)
5. dry with materialdried over Na2SO4
6. concentrationThe solution was concentrated in vacuo
7. customaffording a viscous oil
8. customThe crude product was further purified by flash chromatography (60% EtOAc in hexane)