反应详情

温度

80 °C

(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).

1. extractionextracted with EtOAc (3×10 mL)
2. washThe combined extracts were washed with brine (10 mL)
3. dry with materialdried (Na2SO4)
4. filtrationfiltered
5. concentrationconcentrated in vacuo
6. customThe residue was purified by flash silica gel chromatography (0-30% EtOAc/hexanes gradient)