反应详情

温度

-70 °C

A mixture of DIPA (1.4 mol) in THF (3000 ml) was stirred at −70° C. under N2 flow. Butyllithium 2.5 M/hexane (1.3 mol) was added portionwise at a temperature below −40° C. The mixture was stirred at −70° C. for 15 min. 1-phenylethyl-1H-imidazole (1 mol) dissolved in THF was added dropwise at a temperature below −55° C. The mixture was stirred at −70° C. for 1 hour. 1-(phenylmethyl)-4-piperidinone (1.2 mol) dissolved in THF was added dropwise at a temperature below −55° C. The mixture was stirred at −70° C. for 1 hour, then brought to room temperature, stirred at room temperature overnight and decomposed with H2O. The organic solvent was evaporated. The aqueous concentrate was extracted with CH2Cl2. The organic layer was separated, dried (MgSO4), filtered and the solvent was evaporated. The residue was crystallized from DIPE (1100 ml). The precipitate was filtered off, washed with DIPE and dried, yielding 271 g of 4-[1-(2-phenylethyl)-1H-imidazol-2-yl]-1-(phenylmethyl)-4-piperidinol (75%) (interm. 1).

1. stirringThe mixture was stirred at −70° C. for 15 min
2. additionwas added dropwise at a temperature below −55° C
3. stirringThe mixture was stirred at −70° C. for 1 hour
4. additionwas added dropwise at a temperature below −55° C
5. stirringThe mixture was stirred at −70° C. for 1 hour
6. custombrought to room temperature
7. stirringstirred at room temperature overnight
8. customThe organic solvent was evaporated
9. concentrationThe aqueous concentrate
10. extractionwas extracted with CH2Cl2
11. customThe organic layer was separated
12. dry with materialdried (MgSO4)
13. filtrationfiltered
14. customthe solvent was evaporated
15. customThe residue was crystallized from DIPE (1100 ml)
16. filtrationThe precipitate was filtered off
17. washwashed with DIPE
18. customdried