Hexane → 1-Benzyl-4-(1-phenethyl-1H-imidazol-2-YL)piperidin-4-OL

HRID 7406

Reaction equation

HRID 7406 reaction equation
C([Li])CCC.[CH3:6][CH2:7][CH2:8][CH2:9][CH2:10][CH3:11].[C:12]1([CH:18]([N:20]2[CH:24]=[CH:23][N:22]=[CH:21]2)C)C=CC=CC=1.[C:25]1([CH2:31][N:32]2[CH2:37][CH2:36][C:35](=[O:38])[CH2:34][CH2:33]2)[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1>C1COCC1.O>[C:8]1([CH2:12][CH2:18][N:20]2[CH:24]=[CH:23][N:22]=[C:21]2[C:35]2([OH:38])[CH2:36][CH2:37][N:32]([CH2:31][C:25]3[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=3)[CH2:33][CH2:34]2)[CH:7]=[CH:6][CH:11]=[CH:10][CH:9]=1

Participants

7

Reactant 4

HCID 8058HexaneHCID 192201-Benzyl-4-piperidoneHCID 98153511-(1-Phenylethyl)-1h-imidazoleHCID 178418339Butyllithium

Product 1

HCID 113259041-Benzyl-4-(1-phenethyl-1H-imidazol-2-YL)piperidin-4-OLYield 75%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-70 °C

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-b62c82ce4a9f497c902d1d7f12e1a2c2
Source dataset
uspto-grants-2006_08
Patent number
US07087595B2

Linked notes

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