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

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Reaction Conditions

Reaction Steps

(S)-4-Methyl-2-[methyl-(tetrahydro-pyran-4-yl)-amino]-pentanoic acid (0.200 g, 0.873 mmol, Example 27, 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 (0.304 mL, 1.75 mmol) and solid O-benzotriazol-1-yl-N,N,N′,N′-tetramethyluronium hexafluorophosphate (0.331 g, 0.873 mmol). The resulting reaction mixture was stirred at that temperature for 30 minutes; solid 1-bis(4-fluorophenyl)methyl piperazine (0.252 g, 0.873 mmol) was then added. After stirring for, sequentially, 15 minutes at 0° C. and 40 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 (50% EtOAc in hexane) to provide 0.326 g (75%) of the pure titled compound as a white foam: mp 56-65° C. APCI-MS m/z 500.3 (MH+).

Provenance & Evidence