反应详情

(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[(5′-bromo-4-fluoro-2′-methoxybiphenyl-2-yl)methyl]-4-methyl-1,3-oxazolidin-2-one (50 mg, 0.082 mmol), (2-methylphenyl) boronic acid (22 mg, 0.165 mmol), 1,1′-bis(diphenylphosphino)ferrocene-palladium dichloride dichloromethane adduct (20 mg, 0.024 mmol), aqueous potassium hydroxide (55 μL, 3M, 0.165 mmol) and 1,4-dioxane (1 mL) were placed in a sealed tube and subjected to microwave irradiation at 140° C. for 20 minutes to complete the reaction. The crude reaction mixture was purified by preparative TLC on SiO2 (eluted with 20% Ethyl Acetate in hexanes) to afford (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[(4-fluoro-6′-methoxy-2″-methyl-1,1′:3′,1″-terphenyl-2-yl)methyl]-4-methyl-1,3-oxazolidin-2-one as a colorless glass. LCMS calc.=617.18; found=618.16 (M+1)+. 1H NMR signals are doubled because of atropisomerism 1H NMR (CDCl3, 500 MHz) δ 7.84 (s, 1H), 7.68 (s, 1H), 7.62 (s, 1H), 7.36-7.32 (m, 1H), 7.30-7.22 (m, 4H), 7.22-7.18 (m, 1.5H), 7.18-7.14 (m, 0.5H), 7.14-7.11 (m, 1H), 7.11-7.05 (m, 1H), 7.02 (t, J=8.0 Hz, 1H), 5.58 (d, J=8.5 Hz, 0.55H), 5.28 (d, J=8 Hz, 0.45H), 4.90 (d, J=3.5 Hz, 0.45H), 4.09 (d, J=15.5 Hz, 0.45H), 3.88 (d, J=16.5 Hz, 0.55H), 3.844, 3.838 (s, 3H), 3.82-3.75 (m, 1H), 2.32, 2.56 (s, 3H), 0.52 (d, J=6.5 Hz, 1.35H), 0.38 (d, J=6.5 Hz, 1.65H).

1. customirradiation at 140° C. for 20 minutes
2. customthe reaction
3. customThe crude reaction mixture
4. customwas purified by preparative TLC on SiO2 (eluted with 20% Ethyl Acetate in hexanes)