反应 #7502

反应方程式

1-(phenylmethyl)-4-piperidinone

1-phenylethyl-1H-imidazole

Butyllithium

hexane

→

4-[1-(2-phenylethyl)-1H-imidazol-2-yl]-1-(phenylmethyl)-4-piperidinol

收率 75.0%

溶剂

H2O

THF

THF

THF

反应条件

后处理

1. 1
   workup.STIRRINGThe mixture was stirred at −70° C. for 15 min
2. 2
   workup.ADDITIONwas added dropwise at a temperature below −55° C
3. 3
   workup.STIRRINGThe mixture was stirred at −70° C. for 1 hour
4. 4
   workup.ADDITIONwas added dropwise at a temperature below −55° C
5. 5
   workup.STIRRINGThe mixture was stirred at −70° C. for 1 hour
6. 6
   其他brought to room temperature
7. 7
   workup.STIRRINGstirred at room temperature overnight
8. 8
   其他The organic solvent was evaporated
9. 9
   浓缩The aqueous concentrate
10. 10
    萃取was extracted with CH2Cl2
11. 11
    其他The organic layer was separated
12. 12
    干燥dried (MgSO4)
13. 13
    过滤filtered
14. 14
    其他the solvent was evaporated
15. 15
    其他The residue was crystallized from DIPE (1100 ml)
16. 16
    过滤The precipitate was filtered off
17. 17
    洗涤washed with DIPE
18. 18
    其他dried

实验过程

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).

来源