反应详情

温度

80 °C

At 0° C. under N2, NaH (20 g, 0.500 mol) was added slowly to the mixture of tert-butyl {1-[3,5-bis(trifluoromethyl)phenyl]-1-hydroxybut-3-en-2-yl}carbamate (100 g, 0.250 mol) in anhydrous THF (1.5 L) while stirring. After the addition, the mixture was stirred at 0° C. for 1 hour, then at 80° C. for 2-6 hrs. (Caution: The mixture was stirred and heated at 80° C. for 0.5-1 hour of bubbling). The resulting mixture was cooled to 0° C. and MeOH (0.1 L) and ice water (0.2 L) was added carefully to quench the reaction. The mixture was concentrated and then diluted with ethyl acetate (2 L), washed with water (0.5 L×3), brine (0.5 L), dried and concentrated to give a black oil. Flash chromatography on silica gel yielded the crude product which was recrystallized from ethyl acetate, dichloromethane and petroleum ether to provide cis-5-[3,5-bis(trifluoromethyl)phenyl]-4-ethenyl-1,3-oxazolidin-2-one (25 g) as a white solid. The resultant solid was separated by chiral SFC (column—OJ 250 mm×50 mm, 10 um; mobile phase-A: supercritical CO2, B: IPA, A:B=85:15 at 230 mL/min; column temp: 38° C.; nozzle pressure-100 bar; nozzle temp-60° C.; evaporator temp-20° C.; trimmer temp-25° C.; wavelength-220 nm). 1H NMR (400 MHz, DMSO-d6) δ 8.30 (s, 1H), 8.10 (s, 1H), 7.93 (s, 2H), 6.05-6.03 (d, 1H), 5.27-5.11 (m, 2H), 4.99-4.97 (d, 1H), 4.76-4.73 (t, 1H).

1. additionAfter the addition
2. stirringthe mixture was stirred at 0° C. for 1 hour
3. stirring(Caution: The mixture was stirred
4. customof bubbling)
5. temperatureThe resulting mixture was cooled to 0° C.
6. additionMeOH (0.1 L) and ice water (0.2 L) was added carefully
7. customto quench
8. customthe reaction
9. concentrationThe mixture was concentrated
10. additiondiluted with ethyl acetate (2 L)
11. washwashed with water (0.5 L×3), brine (0.5 L)
12. customdried
13. concentrationconcentrated
14. customto give a black oil
15. customFlash chromatography on silica gel yielded the crude product which
16. customwas recrystallized from ethyl acetate, dichloromethane and petroleum ether