反应详情

To a slurry of Zn powder (3.4 g, 51.5 mmol) in dry tetrahydrofuran (50 mL) was slowly added TiCl4 (2.7 mL, 25.1 mmol) at RT under a nitrogen atmosphere. The reaction mixture was heated at reflux for 2.5 h. To the reaction mixture was added a solution of cycloheptanone (2.4 mL, 20.3 mmol) and (4-bromo-2-fluoro-phenyl)-(4-hydroxy-phenyl)-methanone (76) (2 g, 6.78 mmol) in dry tetrahydrofuran (50 mL). The reaction mixture was heated at reflux for 2 h. The reaction mixture was cooled to room temperature, then water (40 mL) was added followed by 10% K2CO3 (40 mL). The reaction mixture was filtered through a pad of Celite and the pad was washed with EtOAc. The filtrate was transferred to a separatory funnel and the layers were separated. The aqueous layer was extracted with EtOAc and the combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated. The crude material was loaded onto silica gel and purified by flash chromatography with a hexanes:EtOAc gradient (100:0 to 90:10) to give 2.249 (88%) of compound 175. 1H NMR indicates that the product contains ˜3% cycloheptanone. 1H NMR (400 MHz, DMSO-d6): δ 1.43-1.50 (m, 8H), 2.05-2.08 (m, 2H), 2.23-2.24 (m, 2H), 6.65 (d, J=8.4 Hz, 2H), 6.91 (d, J=8.4 Hz, 2H), 7.14, (t, J=8.1 Hz, 1H), 7.32-7.35 (m, 1H), 7.44-7.47 (m, 1H), 9.33 (s, 1H).

1. customat RT
2. temperatureThe reaction mixture was heated
3. temperatureat reflux for 2.5 h
4. temperatureThe reaction mixture was heated
5. temperatureat reflux for 2 h
6. filtrationThe reaction mixture was filtered through a pad of Celite
7. washthe pad was washed with EtOAc
8. customThe filtrate was transferred to a separatory funnel
9. customthe layers were separated
10. extractionThe aqueous layer was extracted with EtOAc
11. washthe combined organic layers were washed with brine
12. dry with materialdried over Na2SO4
13. filtrationfiltered
14. concentrationconcentrated
15. custompurified by flash chromatography with a hexanes