反应详情

温度

0 °C

A suspension of (S)-2-isopropylamino-4-methyl-pentanoic acid (433 mg, 2.50 mmol), N-methylmorpholine (0.275 mL, 2.50 mmol), and 4,4-bis-(4-fluoro-phenyl)-butylamine monohydrochloride (750 mg, 2.52 mmol) in dry DMF (12 mL) was treated with Triton® B (2.27 mL, 4.99 mmol, 40 wt 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 (0.940 g, 2.50 mmol) was then added. After stirring at 0° C. for 90 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 100 mL of diethyl ether; the resulting mixture was successively washed with saturated aqueous NaHCO3 solution (100 mL), brine (100 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). The free amine was dissolved in 5 mL of ethyl ether and treated with ethereal HCl to afford 368 mg (35%) of the pure titled compound as a white foam: mp 100-103° C.

1. customa clear solution was obtained
2. customwas removed
3. waitthe stirring was continued at ambient temperature for 30 minutes
4. waitAfter this period
5. additionthe reaction mixture was mixed with 100 mL of diethyl ether
6. washthe resulting mixture was successively washed with saturated aqueous NaHCO3 solution (100 mL), brine (100 mL)
7. dry with materialwas dried over Na2SO4
8. concentrationThe solution was concentrated in vacuo
9. customaffording a viscous oil
10. customThe crude product was purified by flash chromatography (EtOAc:hexanes:MeOH 50:50:5)
11. dissolutionThe free amine was dissolved in 5 mL of ethyl ether
12. additiontreated with ethereal HCl