反应详情

Acetyl-{3-[4-(1,1-dioxo-hexahydro-1λ6-thiopyran-4-yl)-3-fluoro-phenyl]-2-oxo-oxazolidin-5(R)-ylmethyl}-carbamic acid 1-chloro-ethyl ester (11) (0.40 g, 0.81 mmol) and cesium isonicotinate (0.42 g, 1.64 mmol) in acetonitrile (20 mL) are heated to reflux overnight. After cooling to RT, water is added and the reaction mixture is extracted with EtOAc and then with dichloromethane. The organic phases are washed separately with brine and then the organic layers are combined, dried over MgSO4, filtered, and conc in vacuo. The isolated residue is subjected to silica gel flash chromatography, eluting with MeOH/CH2Cl2 gradient (0-5% MeOH over 1 hour and 20 minutes) to afford the title compound. Isolated yield: 83%. 1H NMR (400 MHz, DMSO-d6): δ 8.78-8.74 (m, 2H), 7.85 (dd, 1H), 7.79 (dd, 1H), 7.40-7.35 (m, 1H), 7.31 (t, 1H), 7.21-7.17 (m, 1H), 7.01-6.94 (m, 1H), 4.79-4.72 (m, 1H), 4.12-4.00 (m, 2H), 3.91-3.84 (m, 1H), 3.78-3.73 (m, 1H), 3.36-3.26 (m, partially obscured by water, 2H), 3.17-3.11 (m, 1H), 3.07-3.03 (m, 2H), 2.40 (d, 3H), 2.15-2.04 (m, 2H), 2.00-1.97 (m, 2H) 1.59 (dd, 3H).

1. temperatureto reflux overnight
2. extractionthe reaction mixture is extracted with EtOAc
3. washThe organic phases are washed separately with brine
4. dry with materialdried over MgSO4
5. filtrationfiltered
6. washeluting with MeOH/CH2Cl2 gradient (0-5% MeOH over 1 hour and 20 minutes)