反应详情

To a solution of lithium bis(trimethylsilyl)amide (1.0 M/THF, 2 eq. 13.6 mL) in THF (15 mL) was added 2,2-dimethylcyclohexanone (1.88 mL, 13.6 mmol) at −78° C. The reaction was stirred for 15 minutes, and then the intermediate obtained in Step A (3 g, 11.4 mmol) was added dropwise. The reaction was stirred overnight and allowed to warm to room temperature. To the crude product was added acetic add (19.4 mL), ammonium acetate (2.62 g, 34.0 mmol) and copper acetate (5.14 g, 28.3 mmol). The reaction mixture was heated at 100° C. and the THF was removed by distillation. The reaction was heated to 130° C. and allowed to reflux for 24 hours. Ethyl acetate (100 mL) was added and washed with sodium bicarbonate (2×30 mL), water (2×20 mL), brine (2×20 mL), dried with MgSO4, filtered, and concentrated to afford an oil. Flash chromatography (5% ethyl acetate/hexane) afforded a white solid (1.36, 3.7 mmol, 32%). 1H NMR (300 MHz, CDCl3): δ 7.17 (m, 2H), 7.08 (m, 2H), 3.98 (q, J=7.4 Hz, 2H), 3.03 (septet, J=7.0 Hz, 1H), 2.35 (t, J=5.9 Hz, 2H), 1.70 (m, 4H), 1.36 (s, 6H), 1.31 (d, J=4.1 Hz, 6H), 0.965 (t, J=7.4 Hz, 3H). FAB-MS: calculated for (C23H28FNO) 369, found 370 (M+H. mp 124-126° C. Rf=0.6 (50% CH2Cl2/hexane).

1. stirringThe reaction was stirred overnight
2. temperatureThe reaction mixture was heated at 100° C.
3. customthe THF was removed by distillation
4. temperatureThe reaction was heated to 130° C.
5. temperatureto reflux for 24 hours
6. additionEthyl acetate (100 mL) was added
7. washwashed with sodium bicarbonate (2×30 mL), water (2×20 mL), brine (2×20 mL)
8. dry with materialdried with MgSO4
9. filtrationfiltered
10. concentrationconcentrated
11. customto afford an oil