反应详情

温度

0 °C

A suspension of (S)-4-methyl-2-(tetrahydro-pyran-4-ylamino)-pentanoic acid (430 mg, 2.00 mmol), N-methylmorpholine (0.220 mL, 2.00 mmol), and 4,4-bis-(4-fluoro-phenyl)-butylamine monohydrochloride (597 mg, 2.00 mmol) in dry DMF (10 mL) was treated with Triton® B (1.82 mL, 4.00 mmol, 40 weight percent solution in methanol, Aldrich, Milwaukee, Wis.), a clear solution was obtained and cooled to 0° C. in an ice-water bath. Solid O-benzotriazol-1-yl-N,N,N′,N′-tetramethyluronium hexafluorophosphate (0.760 g, 2.00 mmol) was then added. After stirring at 0° C. for 30 minutes, was added, the cooling bath was then removed, and the stirring was continued at ambient temperature for 30 minutes. After this period, the reaction mixture was mixed with 50 mL of diethyl ether; the resulting mixture 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 (EtOAc:hexanes:MeOH 50:50:5) to give 300 mg (39%) of the pure titled compound as a clear oil. APCI-MS m/z 459.4 (MH+).

1. customa clear solution was obtained
2. additionwas added
3. customthe cooling bath was then removed
4. waitthe stirring was continued at ambient temperature for 30 minutes
5. waitAfter this period
6. additionthe reaction mixture was mixed with 50 mL of diethyl ether
7. washthe resulting mixture was successively washed with saturated aqueous NaHCO3 solution (50 mL), brine (2×50 mL)
8. dry with materialwas dried over Na2SO4
9. concentrationThe solution was concentrated in vacuo
10. customaffording a viscous oil
11. customThe crude product was purified by flash chromatography (EtOAc:hexanes:MeOH 50:50:5)