4-tert-Butylbenzaldehyde → (S)-2-[(4-tert-Butyl-benzyl)-methyl-amino]-4-methyl-pentanoic acid [4,4-bis-(4-fluoro-phenyl)-butyl]-amide monohydrochloride

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Reaction Steps

(S)-4-Methyl-2-methylamino-pentanoic acid [4,4-bis-(4-fluoro-phenyl)-butyl]-amide monohydrochloride (0.25 g, 0.58 mmol, Example 12) and 4-t-butylbenzaldehyde (94 mg, 0.58 mmol, Aldrich, Milwaukee, Wis.) were mixed in CH2Cl2 (10 mL). After stirring at ambient temperature under nitrogen atmosphere for 30 minutes, the solution was cooled to 0° C. in an ice-water bath. To this solution was added sodium triacetoxyborohydride (0.18 g, 0.87 mmol). The resulting reaction mixture was stirred for, in succession, 30 minutes at 0° C. and 12 hours at ambient temperature. Six milliliters of saturated aqueous NaHCO3 solution 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 (2×10 mL). The combined organic solution was dried over Na2SO4. The solution was concentrated in vacuo affording a viscous oil. The crude product was purified first by flash chromatography (25% EtOAc in hexanes), then by preparative plate (5% acetonitrile in chloroform). The free amine was dissolved in 5 mL of ethyl ether and treated with ethereal HCl to afford 130 mg (42% over 2 steps) of the pure titled compound as a white foam: mp 87-95° C. APCI-MS m/z 535.0 (MH+).

Provenance & Evidence