Hydrochloric Acid → (2R,4S)-5-biphenyl-4-yl-4-(3,5-difluoro-4-hydroxy-benzoylamino)-2-methyl-pentanoic acid

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Reaction Steps

Next, to a solution of (2R,4S)-5-biphenyl-4-yl-4-(3,5-difluoro-4-hydroxy-benzoylamino)-2-methyl-pentanoic acid ethyl ester (30 mg, 0.064 mmol) in MeOH (2 mL) at room temperature is added aqueous 1M NaOH (4 mL, 4.0 mmol). After stirring for 1 hour the reaction is quenched with aqueous 1M HCl (4 mL, 4.0 mmol). The mixture is concentrated under reduced pressure and filtered to remove NaCl salt. The obtained residue is purified by preparative silica gel thin-layer chromatography (7% MeOH in DCM) to give 17.1 mg of (2R,4S)-5-biphenyl-4-yl-4-(3,5-difluoro-4-hydroxy-benzoylamino)-2-methyl-pentanoic acid. HPLC Retention time 1.56 minutes (condition B); MS 440 (M+1); 1H NMR (400 MHz, ACETONITRILE-d3) δ ppm 1.19 (d, J=7.07 Hz, 3H) 1.55 (ddd, J=14.27, 10.74, 3.79 Hz, 1H) 1.90-1.96 (m, 1H) 2.54-2.71 (m, 1H) 2.91 (dd, J=6.69, 3.16 Hz, 2H) 4.25-4.43 (m, 1H) 6.49 (d, J=9.60 Hz, 2H) 6.93 (d, J=8.84 Hz, 1H) 7.33-7.42 (m, 3H) 7.49 (t, J=7.71 Hz, 2H) 7.61 (d, J=8.34 Hz, 2H) 7.67 (dd, J=8.34, 1.26 Hz, 2H).

Provenance & Evidence