反应详情

温度

55 °C

4-fluoro-1-nitro-2-(trifluoromethyl)benzene (8) (901 g, 4.309 mol) was introduced into a 30 L jacketed vessel, along with sodium carbonate (959.1 g, 9.049 mol) and DMSO (5 L, 5.5 vol) under nitrogen atmosphere, with stirring. 7-azabicyclo[2.2.1]heptane hydrochloride (9) (633.4 g, 4.740 mol) was then added to the vessel in portions, and the temperature was gradually raised to 55° C. The reaction was monitored by HPLC, and when the substrate was <1% AUC, the reaction was considered complete. The mixture was then diluted with 10 vol EtOAc and washed with water (5.5 vol) three times. The organic layer was then concentrated to 4 vol and cyclohexane was added and concentrated to 4 vol. The process of adding cyclohexane and concentrating the resulting solution to 4 vol was repeated until all the EtOAc was removed, and the total volume in the flask was about 4 vol containing cyclohexane. The reaction mixture was heated to 60° C. on a rotary evaporator for 30 min. The solution was then cooled to room temperature with stirring or rotation for 3 h. All the solid then crystallized, and was concentrated to dryness to provid 7-[4-nitro-3-(trifluoromethyl)phenyl]-7-azabicyclo[2.2.1]heptane (10A).

1. washwashed with water (5.5 vol) three times
2. concentrationThe organic layer was then concentrated to 4 vol and cyclohexane
3. additionwas added
4. concentrationconcentrated to 4
5. concentrationThe process of adding cyclohexane and concentrating the resulting solution to 4 vol
6. customwas removed
7. additioncontaining cyclohexane
8. temperatureThe reaction mixture was heated to 60° C. on a rotary evaporator for 30 min
9. temperatureThe solution was then cooled to room temperature
10. customAll the solid then crystallized
11. concentrationwas concentrated to dryness