Diethyl Ether → HCID 70156176, compound

Participants

Reaction Conditions

Reaction Steps

(S)-2-(Cyclohexyl-methyl-amino)-4-methyl-pentanoic acid (0.200 g, 0.880 mmol, Example 21, 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 (0.389 mL, 1.76 mmol) and solid O-benzotriazol-1-yl-N,N,N,′,N′-tetramethyluronium hexafluorophosphate (0.334 g, 0.880 mmol). The resulting reaction mixture was stirred at that temperature for 30 minutes; solid 1-bis(4-fluorophenyl)methyl piperazine (0.254 g, 0.880 mmol) was then added. After stirring for, sequentially, 10 minutes at 0° C. and 90 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 (30% EtOAC in hexanes). The free amine was dissolved in 5 mL of ethyl ether and treated with ethereal HCl. Subsequent concentration in vacuo and drying under vacuum provided 0.39 g (78%) of the pure titled compound as a white solid; mp 171-182° C. APCI-MS m/z 498.3 (MH+).

Provenance & Evidence