Acetic Acid → Benzyl 4-(1-(tert-butoxycarbonyl)piperidin-4-yl)piperazine-1-carboxylate

HRID 2265694Notes

Reaction equation

HRID 2265694 reaction equation
[N:1]1([C:7]([O:9][CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[O:8])[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.O=[C:18]1[CH2:23][CH2:22][N:21]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:20][CH2:19]1.C(O)(=O)C>CO.[Pd]>[C:27]([O:26][C:24]([N:21]1[CH2:22][CH2:23][CH:18]([N:4]2[CH2:5][CH2:6][N:1]([C:7]([O:9][CH2:10][C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=3)=[O:8])[CH2:2][CH2:3]2)[CH2:19][CH2:20]1)=[O:25])([CH3:30])([CH3:28])[CH3:29]

Participants

6

Reactant 3

HCID 176Acetic AcidHCID 643495Benzyl piperazine-1-carboxylateHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylate

Product 1

HCID 18971584Benzyl 4-(1-(tert-butoxycarbonyl)piperidin-4-yl)piperazine-1-carboxylateYield 29.6%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

Benzyl 1-piperazinecarboxylate (5.00 g) and tert-butyl 4-oxopiperidine-1-carboxylate (4.52 g) were dissolved in methanol (100 ml), and acetic acid (2.34 ml) and 10% palladium on carbon (1.55 g) were added thereto, followed by stirring under a hydrogen atmosphere for 4 days. The catalyst was removed by filtration, and the filtrate was concentrated. To the residue were added acetone (50 ml) and water (50 ml) to dissolve, and sodium hydrogencarbonate (6.67 g) was added and stirred while cooling in an ice bath. Benzyl chloroformate (3.89 ml) was added thereto, followed by stirring in an ice bath for 3.5 hr. Part of the reaction mixture was concentrated, and ethyl acetate:tetrahydrofuran=1:1 (200 ml) and water (100 ml) were added thereto, followed by stirring at room temperature for 10 min. The organic layer was separated. The organic layer was washed with brine, and dried over anhydrous sodium sulfate. This was concentrated, and the residue was purified by silica gel column chromatography (eluent; ethyl acetate, then ethyl acetate:methanol=50:1). Fractions containing the target compound were concentrated to provide the titled compound as a pale yellow oil (2.71 g, 29.6%).

Workup

  1. customThe catalyst was removed by filtration
  2. concentrationthe filtrate was concentrated
  3. additionTo the residue were added acetone (50 ml) and water (50 ml)
  4. dissolutionto dissolve
  5. additionsodium hydrogencarbonate (6.67 g) was added
  6. stirringstirred
  7. temperaturewhile cooling in an ice bath
  8. additionBenzyl chloroformate (3.89 ml) was added
  9. stirringby stirring in an ice bath for 3.5 hr
  10. concentrationPart of the reaction mixture was concentrated
  11. additionethyl acetate:tetrahydrofuran=1:1 (200 ml) and water (100 ml) were added
  12. stirringby stirring at room temperature for 10 min
  13. customThe organic layer was separated
  14. washThe organic layer was washed with brine
  15. dry with materialdried over anhydrous sodium sulfate
  16. concentrationThis was concentrated
  17. customthe residue was purified by silica gel column chromatography (eluent
  18. additionFractions containing the target compound
  19. concentrationwere concentrated

Sources & evidence

ORD record
ord-3b7cddf311e64e7fbd57ec1b89a958a0
Source dataset
uspto-grants-2010_12
Patent number
US07855290B2

Reaction notes

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