Cyclohexanecarboxaldehyde → (S)-3-(4-Benzyloxy-phenyl)-N-tert-butyl-2-[cyclohexyl-methyl-(3-methyl-butyl)-amino]-propionamide monohydrochloride

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Reaction Steps

(S)-3-(4-Benzyloxy-phenyl)-N-tert-butyl-2-(3-methyl-butylamino)-propionamide mono-hydrochloride (1.0 g, 2.3 mmol, Example 2) and cyclohexanecaboxaldehyde (0.28 g, 2.3 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 (0.73 g, 3.4 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 (20% EtOAc in hexanes). The free amine was dissolved in 10 mL of ethyl ether and treated with ethereal HCl to afford 0.70 g (58%) of the pure titled compound as a white foam; mp 70-81° C.

Provenance & Evidence