Diisopropylethylamine → (s)-4-Phenyl-piperazine-1-carboxylic acid (1-{4-[bis-(4-fluoro-phenyl)-methyl]-piperazine-1-carbonyl}-3-methyl-butyl)-amide

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Reaction Conditions

Reaction Steps

(S)-4-Methyl-2-[(4-phenyl-piperazine-1-carbonyl)-amino]pentanoic acid (0.300 g, 0.939 mmol, Example 17, Step B) 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 (0.327 mL, 1.88 mmol) and solid O-benzotriazol-1-yl-N,N,N′,N′-tetramethyluronium hexafluorophosphate (0.356 g, 0.939 mmol). The resulting reaction mixture was stirred at that temperature for 35 minutes; solid 1-bis(4-fluorophenyl)methyl piperazine (0.271 g, 0.939 mmol) was then added. After stirring for, sequentially, 10 minutes at 0° C. and 40 minutes at ambient temperature, reaction mixture was mixed with 60 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, then 60% EtOAc in hexane) to provide 0.42 g (76%) of the pure titled compound as a light yellow foam: mp 83-91 ° C. APCI-MS m/z 590.4 (MH+).

Provenance & Evidence