Potassium tert-butoxide → (4S,6S)-6-[3,5-bis(trifluoromethyl)phenyl]-3-{[4'-fluoro-5'-isopropyl-2'-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}-4-methyl-1,3-oxazinan-2-one

Participants

Reaction Steps

To a stirred solution of 2′-(bromomethyl)-4-fluoro-5-isopropyl-2-methoxy-4′-(trifluoromethyl)biphenyl (Intermediate 13; 61.7 mg; 0.152 mmol) and (4S,6S)-6-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-1,3-oxazinan-2-one (Intermediate 22; 41.5 mg; 0.127 mmol) in DMF (1 mL) under an atmosphere of N2 was added potassium tert-butoxide (14.2 mg; 0.127 mmol). The reaction stirred at room temperature for 1 h and was quenched with sat. NH4Cl. The reaction was partitioned between EtOAc (15 mL) and sat. NH4Cl (10 mL). The aqueous layer was re-extracted with EtOAc (4×25 mL), and the combined extracts were washed with brine, dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by flash silica gel chromatography (0-10% EtOAc/hexanes gradient) to afford (4S,6S)-6-[3,5-bis(trifluoromethyl)phenyl]-3-{[4′-fluoro-5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}-4-methyl-1,3-oxazinan-2-one as a white solid. LCMS=652.3 (M+1)+. 1H NMR (CDCl3, 500 MHz, mixture of atropsiomers): δ 7.87 (s, 2H), 7.79 (s, 1H), 7.65 (s, 1H), 7.62-7.59 (m, 1H), 7.36-7.32 (m, 1H), 7.03 (d, J=10.9 Hz, 1H), 6.70 (d, J=11.9 Hz, 1H), 5.21 (d, J=10.5 Hz, 1H), 5.10 (d, J=16.3 Hz, 1H), 4.39 (d, J=16 Hz, 1H), 3.78 (s, 3H), 3.45-3.37 (m, 1H), 3.25-3.18 (m, 1H), 2.32-2.22 (m, 1H), 1.91-1.78 (m, 1H), 1.27-1.21 (m, 6H), 1.02 (d, J=6.2 Hz, 3H).

Provenance & Evidence