Hydrochloric Acid → (S)-3-(4-Benzyloxy-phenyl)-N-tert-butyl-2-(3-methyl-butylamino)-propionamide monohydrochloride

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Reaction Steps

(S)-2-amino-3-(4-benzyloxy-phenyl)-N-tert-butyl-propionamide monohydrochloride (5.0 g, 14 mmol, Example 2, Step A) and isovaleraldehyde (1.5 mL, 14 mmol, Aldrich, Milwaukee, Wis.) were mixed in CH2Cl2 (70 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 (4.4 g, 21 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 (100 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 (2×70 mL). The combined organic solution was dried over Na2SO4. TLC (70% EtOAc in Hexanes as the eluant) showed two spots with Rf values of 0.84 and 0.51. The solution was concentrated in vacuo affording a viscous oil. The lower spot on the TLC (Rf=0.51) was isolated by flash chromatography (50% EtOAc in hexanes). The free amine was dissolved in 20 mL of ethyl ether and treated with ethereal HCl to afford 3.67 g (62%) of the pure titled compound as a white solid; mp 182-184° C.

Provenance & Evidence