反应详情

n-Butyllithium (1.6 Mol solution in hexanes, 10.3 mL) was added slowly to a stirred, cooled (0° C.) suspension of methyl triphenylphosphonium bromide (5.86 g, 16.4 mmol) in tetrahydrofuran (60 mL) and the mixture was stirred at room temperature for 3 hours. The mixture was cooled to 0° C. and (RS)-α-methyl-N-(4-oxo-1-phenylcyclohexyl)-3,5-bis(trifluoromethyl)benzeneacetamide (Example 3, 3.0 g, 6.56 mmol) in tetrahydrofuran (20 mL) was added. The mixture was stirred at room temperature for 1 hour, then under reflux for 3 hours. The mixture was cooled, poured into water and extracted with ethyl acetate. The combined organic fractions were dried (MgSO4) and the solvent was evaporated under reduced pressure. The residue was purified by chromatography on a short column of silica gel, eluting with dichloromethane, to give the title compound as a colorless solid (2.27 g, 91%). 1H NMR (400 MHz, CDCl3) δ 7.80 (1H, s), 7.75 (2H, s), 7.26–7.20 (5H, m), 5.59 (1H, s), 4.68 (2H, m), 3.70 (1H, d, J 7.1 Hz), 2.53–2.45 (1H, m), 2.38–2.31 (1H, m), 2.29–2.04 (4H, m), 2.00–1.85 (2H, m), and 1.52 (3H, d, J, 7.1 Hz).

1. temperaturecooled
2. temperatureThe mixture was cooled to 0° C.
3. stirringThe mixture was stirred at room temperature for 1 hour
4. temperatureunder reflux for 3 hours
5. temperatureThe mixture was cooled
6. extractionextracted with ethyl acetate
7. dry with materialThe combined organic fractions were dried (MgSO4)
8. customthe solvent was evaporated under reduced pressure
9. customThe residue was purified by chromatography on a short column of silica gel
10. washeluting with dichloromethane