反応 #7502

反応方程式

1-(phenylmethyl)-4-piperidinone

1-phenylethyl-1H-imidazole

Butyllithium

hexane

→

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

収率 75.0%

溶媒

H2O

THF

THF

THF

反応条件

後処理

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
   その他brought to room temperature
7. 7
   workup.STIRRINGstirred at room temperature overnight
8. 8
   その他The organic solvent was evaporated
9. 9
   濃縮The aqueous concentrate
10. 10
    抽出was extracted with CH2Cl2
11. 11
    その他The organic layer was separated
12. 12
    乾燥dried (MgSO4)
13. 13
    ろ過filtered
14. 14
    その他the solvent was evaporated
15. 15
    その他The residue was crystallized from DIPE (1100 ml)
16. 16
    ろ過The precipitate was filtered off
17. 17
    洗浄washed with DIPE
18. 18
    その他dried

実験手順

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).

出典