Ethanol → (2R,4S)-4-amino-5-(biphenyl-4-yl)-2-methylpentanoic acid ethyl ester hydrochloride

Participants

Reaction Steps

150 g (2R,4S)-5-biphenyl-4-yl-4-tert-butoxycarbonylamino-2-methylpentanoic acid (3-a, R1=BOC, R2=R3=H) were dissolved in 1500 ml ethanol at 70° C. 43 ml of thionyl chloride were then added over about 1 hour. The mixture was then stirred for a further 2 hours. The mixture was concentrated to dryness and then suspended in 3400 ml heptane. The precipitate was collected by filtration, yielding 133 g of (2R,4S)-4-amino-5-biphenyl-4-yl-2-methylpentanoic acid ethyl ester hydrochloride (3-a, R1=R2=H, R3=Et). 1H-NMR (DMSO): 1.05 (3H, t, 1-CH3); 1.08 (3H, t, CH2CH3); 1.61 (1H, m, 3-CHH); 1.85 (1H, m, 3-CHH); 2.74 (1H, m, 2-CH); 2.81 (1H, dd, 5-CHH); 3.08 (1H, dd, 5-CHH); 3.36 (1H, m, 4-CH); 3.95 (2H, q, CH2CH3); 7.31 (1H, m, aromatic); 7.35 (2H, m, aromatic); 7.43 (2H, m, aromatic); 7.62 (4H, m, aromatic); 8.30 (3H, s, NH3+). m/z 312 (MN+, 100%)

Provenance & Evidence