Potassium Hydroxide → 2''-({(4S,6S)-6-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazinan-3-yl}methyl)-4'-methoxy-2-methyl-4''-(trifluoromethyl)-1,1':3',1''-terphenyl-4-carboxylic acid

Participants

Reaction Steps

To a stirred solution of methyl 2″-({(4S,6S)-6-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazinan-3-yl}methyl)-4′-methoxy-2-methyl-4″-(trifluoromethyl)-1,1′:3′,1″-terphenyl-4-carboxylate (Step A; 48 mg; 0.065 mmol) in MeOH (5 mL), was added 4 M KOH (800 μL). The reaction was stirred at room temperature for 4 h, quenched with saturated citric acid and partitioned between EtOAc (25 mL) and water (25 mL). The aqueous layer was extracted with EtOAc (3×25 mL) and the combined extracts were washed with brine, dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by preparatory thin layer chromatography, eluting with 2:1 hexanes:EtOAc+1% AcOH to afford 2″-({(4S,6S)-6-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazinan-3-yl}methyl)-4′-methoxy-2-methyl-4″-(trifluoromethyl)-1,1′:3′,1″-terphenyl-4-carboxylic acid as a white solid. LCMS=725.9 (M+1)+. 1H NMR (CDCl3, 500 MHz, mixture of atropisomers) δ 7.97-7.94 (m, 1H), 7.86-7.82 (m, 2H), 7.78 (d, J=8 Hz, 1H), 7.68-7.66 (m, 1H), 7.63-7.61 (m, 1H), 7.45-7.39 (m, 2H), 7.34 (d, J=8 Hz, 1H), 7.25-7.20 (m, 2H), 7.12-7.09 (m, 1H), 5.37 (d, J=15.5 Hz, 1H), 4.67 (d, J=11.4 Hz, 1H), 4.34 (d, J=15.6 Hz, 1H), 3.91 (s, 3H), 3.32-3.26 (m, 1H), 2.36 (s, 3H), 2.19-2.13 (m, 1H), 1.75-1.67 (m, 1H), 1.09 (d, J=6.1 Hz, 3H).

Provenance & Evidence