Diisoamyl ketone → (S)-3-(4-Benzyloxy-phenyl)-N-tert-butyl-2-[4-methyl-1-(3-methyl-butyl)-pentylamino]-propionamide monohydrochloride

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Reaction Steps

(S)-2-Amino-3-(4-benzyloxy-phenyl)-N-tert-butyl-propionamide monohydrochloride (1.04 g, 2.87 mmol, Example 2, Step A) and diisoamyl ketone (0.490 g, 2.87 mmol, Aldrich, Milwaukee, Wis.) were mixed in CH2Cl2 (25 mL). After stirring at ambient temperature under a nitrogen atmosphere for 30 minutes, the solution was cooled to 0° C. in an ice-water bath. To this solution was added sodium triacetoxyborohydride (0.910 g, 4.30 mmol). The resulting reaction mixture was stirred for 30 minutes at 0° C., followed by an additional 12 hours at ambient temperature. Saturated aqueous NaHCO3 solution (25 mL) was added to the reaction mixture, and the resulting mixture was stirred for 5 minutes. The two layers were separated, and the aqueous layer was extracted with CH2Cl2 (2×30 mL). The combined organic solution was dried over Na2SO4. The solution was concentrated in vacuo affording a viscous oil. The crude product was further purified by flash chromatography (25% EtOAc in hexanes). The free amine was dissolved in 10 mL of ethyl ether and treated with ethereal HCl to afford 0.45 g (30%) of the pure titled compound as a white solid; mp 114-115° C.

Provenance & Evidence