反应详情

温度

-20 °C

3-Nitro-5-trifluoromethyl-phenol (8.81 g) was dissolved in THF (76 ml). 1-Boc-4-hydroxy-piperidine (8.81 g, Aldrich) and Ph3P (11.15 g) were added and the solution was cooled to −20° C. A solution of DEAD (6.8 ml, Aldrich) in THF (36 ml) was added dropwise, maintaining the temperature between −20 and −10° C. The reaction was warmed to RT and stirred overnight. The reaction was concentrated in vacuo and triturated with hexane. The yellow solid was removed by filtration and washed with Et2O (25 ml), and hexane. The white filtrate was washed with 1N NaOH (2×), brine (1×) and the hexane layer was dried over Na2SO4, filtered and concentrated in vacuo. The crude material was purified with flash chromatography (SiO2, 5-10% EtOAc/hexane) to obtain 1-Boc-4-(3-nitro-5-trifluoromethyl-phenoxy)-piperidine.

1. temperaturemaintaining the temperature between −20 and −10° C
2. temperatureThe reaction was warmed to RT
3. concentrationThe reaction was concentrated in vacuo
4. customtriturated with hexane
5. customThe yellow solid was removed by filtration
6. washwashed with Et2O (25 ml), and hexane
7. washThe white filtrate was washed with 1N NaOH (2×), brine (1×)
8. dry with materialthe hexane layer was dried over Na2SO4
9. filtrationfiltered
10. concentrationconcentrated in vacuo
11. customThe crude material was purified with flash chromatography (SiO2, 5-10% EtOAc/hexane)