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

Participants

Reaction Conditions

Reaction Steps

(4S,6S)-6-[3,5-bis(trifluoromethyl)phenyl]-3-[2-iodo-5-(trifluoromethyl)benzyl]-4-methyl-1,3-oxazinan-2-one (Intermediate 23; 25 mg; 0.041 mmol), (5-tert-butyl-2-methoxyphenyl)boronic acid (11.1 mg; 0.053 mmol), 1-1′-bis(di tert-butylphosphino)ferrocene palladium dichloride (2.7 mg; 0.0041 mmol), 1 N K2CO3 (1.2 mL) and THF (1.2 mL) were combined in a sealed tube and heated at 80° C. for 1.5 h. The reaction was diluted with H2O (10 mL) and extracted with EtOAc (3×10 mL). The combined extracts were washed with brine (10 mL), dried (Na2SO4), filtered and concentrated in vacuo. The residue was purified by flash silica gel chromatography (0-30% EtOAc/hexanes gradient) to afford (4S,6S)-6-[3,5-bis(trifluoromethyl)phenyl]-3-{[5′-tert-butyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}-4-methyl-1,3-oxazinan-2-one as a white solid. LCMS=648.0 (M+1)+. 1H NMR (CDCl3, 500 MHz, mixture of atropisomers): δ 7.86-7.83 (m, 2H), 7.78 (s, 1H), 7.68 (s, 1H), 7.63-7.59 (m, 1H), 7.44-7.36 (m, 2H), 7.18 (dd, J=6.7, 2.4 Hz, 1H), 6.94 (d, J=8.7 Hz, 1H), 5.20 (d, J=16 Hz, 1H), 5.16 (d, J=11.2 Hz, 1H), 4.38 (d, J=15.8 Hz, 1H), 3.80 (s, 3H), 3.41-3.34 (m, 1H), 2.29-2.24 (m, 1H), 1.88-1.81 (m, 1H), 1.32 (s, 9H), 1.02 (d, J=6.2 Hz, 3H).

Provenance & Evidence