Diisopropylethylamine → (S)-1-{4-[Bis-(4-fluoro-phenyl)-methyl]-piperazin-1-yl}-4-methyl-2-morpholin-4-yl-pentan-1-one

Participants

Reaction Conditions

Reaction Steps

4-Methyl-2-morpholin-4-yl-pentanoic acid (0.200 g, 0.994 mmol, Example 23, Step A) 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 (0.346 mL, 1.99 mmol) and solid O-benzotriazol-1-yl-N,N,N′,N′-tetramethyluronium hexafluorophosphate (0.379 g, 0.994 mmol). The resulting reaction mixture was stirred at that temperature for 30 minutes; solid 1-bis(4-fluorophenyl)methyl piperazine (0.287 g, 0.994 mmol) was then added. After stirring for, sequentially, 10 minutes at 0° C. and 20 minutes at ambient temperature, reaction mixture was mixed with 50 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 a viscous oil. The crude product was further purified by flash chromatography (40% EtOAc in hexane) to provide 0.284 g (60%) of the pure titled compound as a white foam; mp 55-63° C. APCI-MS m/z 472.3.0 (MH+).

Provenance & Evidence