2-Butene, 1-bromo-3-methyl- → (S)-4-Methyl-2-(3-methyl-but-2-enylamino)-pentanoic acid [4,4-bis-(4-fluoro-phenyl)-butyl]-amide monohydrochloride

Participants

Reaction Conditions

Reaction Steps

To a solution of (S)-2-amino-4-methyl-pentanoic acid [4,4-bis-(4-fluoro-phenyl)-butyl]-amide monohydrochloride (0.36 g, 0.88 mmol, Example 7) in THF (15 mL) were added, in succession, N,N-diisopropylethylamine (0.30 mL, 1.7 mmol) and 1-bromo-3-methyl-2-butene (0.10 mL, 0.87 mmol) at ambient temperature under nitrogen atmosphere. The resulting reaction mixture was stirred for 12 hours at that temperature, 16 hours at 50° C., cooled to ambient temperature, and concentrated in vacuo. The desired product was purified by flash chromatography (50% EtOAc in hexanes) and was dissolved in 10 mL of ethyl ether. To this solution was added saturated HCl solution in ethyl ether until no more white precipitate formed. Filtration and drying overnight under vacuum afforded 0.14 g (36%) of the titled compound as a yellow foam; mp 58-72° C. APCI-MS m/z 443.3 (MH+).

Provenance & Evidence