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

HRID 1631971Notes

Reaction equation

HRID 1631971 reaction equation
C([BH3-])#N.[Na+].O=[C:6]1[CH2:11][CH2:10][N:9]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:8][CH2:7]1.[CH2:19]1[NH:24][CH2:23][CH2:22][N:21]([C:25]([O:27][CH2:28][C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)=[O:26])[CH2:20]1.C(O)(=O)C>CO>[C:15]([O:14][C:12]([N:9]1[CH2:10][CH2:11][CH:6]([N:24]2[CH2:19][CH2:20][N:21]([C:25]([O:27][CH2:28][C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)=[O:26])[CH2:22][CH2:23]2)[CH2:7][CH2:8]1)=[O:13])([CH3:18])([CH3:17])[CH3:16]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 643495Benzyl piperazine-1-carboxylateHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 5003444Sodium cyanoborohydride

Product 1

HCID 18971584Benzyl 4-(1-(tert-butoxycarbonyl)piperidin-4-yl)piperazine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

1.89 g (30.1 mmol) of sodium cyanoborohydride were added to a stirred solution of 3.00 g (15.1 mmol) of tert-butyl 4-oxo-1-piperidinecarboxylate and 3.48 g (15.8 mmol) of 1-Z-piperazine in methanol (60 ml) at room temperature. The pH of the solution was adjusted to about pH 7 by dropwise addition of acetic acid and was monitored during the course of the reaction. The reaction mixture was stirred at room temperature overnight and then concentrated in vacuo. The residue was mixed with water (60 ml) and extracted with dichloromethane (4×60 ml). The combined organic phases were washed with saturated NaCl solution, dried over magnesium sulfate and concentrated in vacuo. The residue was purified by chromatography on silica gel (mobile phase gradient 3-10% methanol in dichloromethane). Yield: 3.41 g (56%) of colorless oil

Workup

  1. customwas monitored during the course of the reaction
  2. concentrationconcentrated in vacuo
  3. additionThe residue was mixed with water (60 ml)
  4. extractionextracted with dichloromethane (4×60 ml)
  5. washThe combined organic phases were washed with saturated NaCl solution
  6. dry with materialdried over magnesium sulfate
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by chromatography on silica gel (mobile phase gradient 3-10% methanol in dichloromethane)

Sources & evidence

ORD record
ord-fc7c907feea64a59b0cc329f31056fce
Source dataset
uspto-grants-2014_07
Patent number
US08791148B2

Reaction notes

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