反应详情

温度

0 °C

A suspension of (S)-2-cyclohexylamino-4-methyl-pentanoic acid (0.556 g, 2.62 mmol) and 1-bis(4-fluorophenyl)methyl piperazine (0.378 g, 1.31 mmol) in dry DMF (7 mL) was treated with Triton® B (2.40 mL, 5.28 mmol, 40 weight percent solution in methanol), a clear solution was obtained. The resulting reaction solution was cooled to 0° C. in an ice-water bath. To this solution was added solid O-benzotriazol-1-yl-N,N,N′,N′-tetramethyluronium hexafluorophosphate (0.993 g, 2.62 mmol). After stirring at 0° C. for 30 minutes, the cooling bath was removed, and the stirring was continued at ambient temperature for 30 minutes. After this period, the reaction mixture was mixed with 60 mL of diethyl ether and 60 mL of saturated aqueous NaHCO3 solution. White solid which forms was removed by filtration. The two layers of the filtrate were separated; the organic layer was successively washed with saturated aqueous NaHCO3 solution (50 mL), brine (2×50 mL), and was dried over Na2SO4. The solution was concentrated in vacuo affording a viscous oil. The crude product was purified by flash chromatography (30% EtOAc in hexanes) affording 0.48 g (76%) of the pure titled compound as a white foam: mp 45-54° C. APCI-MS m/z 484.4 (MH+).

1. customa clear solution was obtained
2. customThe resulting reaction solution
3. customthe cooling bath was removed
4. waitthe stirring was continued at ambient temperature for 30 minutes
5. waitAfter this period
6. additionthe reaction mixture was mixed with 60 mL of diethyl ether and 60 mL of saturated aqueous NaHCO3 solution
7. customWhite solid which forms was removed by filtration
8. customThe two layers of the filtrate were separated
9. washthe organic layer was successively washed with saturated aqueous NaHCO3 solution (50 mL), brine (2×50 mL)
10. dry with materialwas dried over Na2SO4
11. concentrationThe solution was concentrated in vacuo
12. customaffording a viscous oil
13. customThe crude product was purified by flash chromatography (30% EtOAc in hexanes)