Piperazine → HCID 131724190, compound

HRID 478441Notes

Reaction equation

HRID 478441 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][C:11](=O)[CH:10]([C:15]2[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][CH:16]=2)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH:22]1[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]1.C([BH3-])#N.[Na+].[OH-].[Na+]>C(O)C.O>[CH2:1]([N:8]1[CH2:13][CH2:12][C@H:11]([N:22]2[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]2)[C@H:10]([C:15]2[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][CH:16]=2)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 4837PiperazineHCID 14798Sodium HydroxideHCID 5003444Sodium cyanoborohydrideHCID 18001162HCID 18001162, compound

Product 1

HCID 131724190HCID 131724190, compoundYield 67%

Reagents, catalysts & solvents 2

HCID 702EthanolSolvent2×HCID 962WaterSolvent2×

Procedure

To a mixture of 1-benzyl-3-(4-chloro-phenyl)-piperidin-4-one (15.2 g, 38.5 mmol) and piperazine (6.78 g, 77.1 mmol) in ethanol (6 mL) was added tetraisopropyl-orthotitanate (22.8 mL, 77.1 mmol) at room temperature. After stirring at room temperature for 3 days the reaction mixture was diluted with ethanol (250 mL) and sodium cyanoborohydride (5.10 g, 77.1 mmol) was added. The reaction mixture was stirred at room temperature for 24 h and was diluted with water (30 mL). The inorganic precipitate was filtered off and washed with ethanol and dichloromethane. The solvent was evaporated and the residue was taken up in ethylenglycol (100 mL) and sodium hydroxide (3.08 g, 77.1 mmol) was added. The reaction mixture was stirred at 130° C. for 15 min. After cooling water (200 mL) was added and the mixture was extracted four times with 200 mL tert.-butyl methyl ether. Organic phases were pooled, dried with magnesium sulfate and evaporated. Flash chromatography on silica gel with methylene chloride/methanol/triethyl amine 98:1:1 gave rac-cis-1-[1-benzyl-3-(4-chloro-phenyl)-piperidin-4-yl]-piperazine (9.54 g, 67%) as a yellow oil, MS: m/e=336.3 (M+H+).

Workup

  1. additionwas added tetraisopropyl-orthotitanate (22.8 mL, 77.1 mmol) at room temperature
  2. additionwas added
  3. stirringThe reaction mixture was stirred at room temperature for 24 h
  4. filtrationThe inorganic precipitate was filtered off
  5. washwashed with ethanol and dichloromethane
  6. customThe solvent was evaporated
  7. stirringThe reaction mixture was stirred at 130° C. for 15 min
  8. additionwas added
  9. extractionthe mixture was extracted four times with 200 mL tert.-butyl methyl ether
  10. dry with materialdried with magnesium sulfate
  11. customevaporated

Sources & evidence

ORD record
ord-f032dac5c2654cbf87e2864cfd72f1ee
Source dataset
uspto-grants-2003_11
Patent number
US06642226B2

Reaction notes

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