反应详情

温度

5 °C

To EtMgBr (344 mL) in THF cooled to −78° C. was added Ti(OiPr)4 (39 g, 137.93 mmol), followed by commercially available 4-benzyl-3-oxo-piperazine-1-carboxylic acid tert-butyl ester (40 g, 137.93 mmol) and the resultant reaction mixture was heated to reflux for 1 h. After cooling the reaction mixture to 5° C., another portion of EtMgBr (344 ml) and Ti(OiPr)4 (39 g, 137.93 mmol) was added. The mixture was stirred for 16 h at RT. The reaction mixture was quenched with NH4Cl solution and stirred for 15 min and filtered through a celite bed and washed with EtOAc. The aqueous layer was again extracted with EtOAc (3×). The combined EtOAc layers were washed with water and dried over Na2SO4 and concentrated under reduced pressure. Purification by column chromatography to afforded the title compound as a solid (24 g, 58%).

1. customthe resultant reaction mixture
2. temperaturewas heated
3. temperatureto reflux for 1 h
4. customThe reaction mixture was quenched with NH4Cl solution
5. stirringstirred for 15 min
6. filtrationfiltered through a celite bed
7. washwashed with EtOAc
8. extractionThe aqueous layer was again extracted with EtOAc (3×)
9. washThe combined EtOAc layers were washed with water
10. dry with materialdried over Na2SO4
11. concentrationconcentrated under reduced pressure
12. customPurification by column chromatography