Reaction Steps
Next, to a solution of (4S)-ethyl 5-(3′-chlorobiphenyl-4-yl)-4-(2-ethyloxazole-5-carboxamido)-2-methylpentanoate (264 mg, 0.56 mmol) in MeOH (2 mL) is added aqueous 1N NaOH (4 mL) After stirring at room temperature for 2 hours, the crude is concentrated under reduced pressure to remove MeOH and is diluted with EtOAc, the organic layer is washed with brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The obtained residue is purified by RP-HPLC (SunFire C18, H2O(0.1% TFA)/CH3CN) and then is purified by chiral-HPLC(OJ-H, 15% EtOH(0.1% TFA)/Heptane), and then lyophilized to give (2S,4S)-5-(3′-chlorobiphenyl-4-yl)-4-(2-ethyloxazole-5-carboxamido)-2-methylpentanoic acid (43 mg), HPLC retention time=1.63 minutes (condition B); MS (m+1)=441.2; 1 H NMR (400 MHz, CD3OD) δ ppm 1 H NMR (400 MHz, CD3OD) δ ppm 1.17 (d, J=7.1 Hz, 3 H) 1.35 (t, J=7.7 Hz, 3 H) 1.69 (ddd, J=14.0, 8.3, 3.9 Hz, 1 H) 2.06 (ddd, J=14.1, 10.8, 5.9 Hz, 1 H) 2.39-2.55 (m, 1 H) 2.85 (q, J=7.6 Hz, 2 H) 2.90 (dd, J=13.4, 7.6 Hz, 1 H) 2.95 (dd, J=13.1, 5.8 Hz, 1 H) 4.31-4.52 (m, 1 H) 7.26-7.35 (m, 3 H) 7.38 (t, J=7.8 Hz, 1 H) 7.46-7.55 (m, 4 H) 7.57 (t, J=1.9 Hz, 1 H) and (2R,4S)-5-(3′-chlorobiphenyl-4-yl)-4-(2-ethyloxazole-5-carboxamido)-2-methylpentanoic acid (60 mg). HPLC retention time=1.62 minutes (condition B); MS (m+1)=441.2; 1 H NMR (400 MHz, CD3OD) δ ppm 1.18 (d, J=7.1 Hz, 3 H) 1.35 (t, J=7.6 Hz, 3 H) 1.69 (ddd, J=14.1, 10.4, 4.3 Hz, 1 H) 2.01 (ddd, J=14.0, 10.0, 3.8 Hz, 1 H) 2.46-2.63 (m, 1 H) 2.85 (q, J=7.6 Hz, 2 H) 2.91 (d, J=7.1 Hz, 2 H) 4.30-4.49 (m, 1 H) 7.26-7.34 (m, 3 H) 7.38 (t, J=7.8 Hz, 1 H) 7.46-7.52 (m, 3 H) 7.52 (s, 1 H) 7.56 (t, J=1.9 Hz, 1 H) 8.31 (d, J=9.1 Hz, 1 H).
