Piperazine → HCID 22141345, compound

HRID 1826406Notes

Reaction equation

HRID 1826406 reaction equation
[CH3:1][C:2]1([C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([N+:25]([O-:27])=[O:26])[CH:20]=2)[N:7]2[CH:3]1[C:4](=O)[CH:5]([CH2:9][CH2:10][CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[C:6]2=O.[BH4-].[Na+].B(F)(F)F.N1CCNCC1>O1CCCC1>[N+:25]([C:21]1[CH:20]=[C:19]([C:2]2([CH3:1])[N:7]3[CH:3]2[CH2:4][CH:5]([CH2:9][CH2:10][CH2:11][C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=2)[CH2:6]3)[CH:24]=[CH:23][CH:22]=1)([O-:27])=[O:26]

Participants

6

Reactant 4

HCID 4837PiperazineHCID 6356Boron trifluorideHCID 4311764Sodium borohydrideHCID 22141333HCID 22141333, compound

Product 1

HCID 22141345HCID 22141345, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Or Method B: (i) To a stirred solution of 6-methyl-6-(3-nitrophenyl)-3-(3-phenylpropyl)azabicyclo[3.1.0]hexane-2,4-dione (Preparation 136, 15.0 g, 41.2 mmol) in tetrahydrofuran (60 ml) under nitrogen was added sodium borohydride (3.27 g, 86.4 mmol) and the reaction mixture was stirred at room temperature for 1 h. The reaction mixture was cooled to between 0° C. and 5° C. and borontrifluoride diethyletherate (16.36 g, 115 mmol) was added. The reaction mixture was allowed to warm to room temperature over 2 h before being heated under reflux for a further 2 h. The reaction mixture was cooled to between 0° C. and 5° C. and an aqueous solution of piperazine (20.92 g in 120 ml) was added. The reaction mixture was then heated under reflux for 18 h. The tetrahydrofuran was removed by distillation and the reaction mixture was allowed to cool to 50° C. Ethyl acetate (90 ml) was added and the resulting biphasic mixture was allowed to cool to room temperature. The phases were separated and the organic extract was washed water (3×60 ml) to afford a solution of 6-(3-nitrophenyl)-6-methyl-3-(3-phenylpropyl)azabicyclo[3.1.0]hexane in ethyl acetate. (ii) To the reaction mixture was added 5% palladium on charcoal (Johnsson Matthey type 87, 1.5 g) and the reaction mixture was placed under an atmosphere of hydrogen (60 psi) at 25° C. for 16 h. The catalyst was removed by filtration through Celite™ and the filtrate was concentrated in vacuo to afford the title compound as a yellow oil which crystallised on standing (11.09 g, 88%).

Workup

  1. temperatureThe reaction mixture was cooled to between 0° C. and 5° C.
  2. temperatureto warm to room temperature over 2 h
  3. temperaturebefore being heated
  4. temperatureunder reflux for a further 2 h
  5. temperatureThe reaction mixture was cooled to between 0° C. and 5° C.
  6. temperatureThe reaction mixture was then heated
  7. temperatureunder reflux for 18 h
  8. customThe tetrahydrofuran was removed by distillation
  9. temperatureto cool to 50° C
  10. additionEthyl acetate (90 ml) was added
  11. temperatureto cool to room temperature
  12. customThe phases were separated
  13. extractionthe organic extract
  14. washwas washed water (3×60 ml)

Sources & evidence

ORD record
ord-30e544b5572c4e0184f1d61d9bd910ea
Source dataset
uspto-grants-2006_05
Patent number
US07049444B2

Reaction notes

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