Sodium Bicarbonate → tert-Butyl 3-(4-benzylpiperazin-1-yl)piperidine-1-carboxylate

HRID 1631977Notes

Reaction equation

HRID 1631977 reaction equation
Cl.[CH2:2]([N:9]([CH2:13][CH2:14]Cl)[CH2:10][CH2:11]Cl)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.Cl.[NH2:17][CH:18]1[CH2:23][CH2:22][CH2:21][N:20]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:19]1.C(=O)(O)[O-].[Na+]>C(O)C>[CH2:2]([N:9]1[CH2:13][CH2:14][N:17]([CH:18]2[CH2:23][CH2:22][CH2:21][N:20]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:19]2)[CH2:11][CH2:10]1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1

Participants

5

Reactant 3

HCID 516892Sodium BicarbonateHCID 2777881N,N-Bis(2-chloroethyl)benzylamine hydrochlorideHCID 177503343-Aminopiperidine hydrochloride, N1-BOC protected

Product 1

HCID 86642500tert-Butyl 3-(4-benzylpiperazin-1-yl)piperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

4.90 g (21.1 mmol) of benzylbis(2-chloroethyl)amine hydrochloride were dissolved in ethanol (120 ml) and, while stirring, 5.00 g (21.1 mmol) of tert-butyl 3-aminopiperidine-1-carboxylate hydrochloride and 14.2 g (169 mmol) of sodium bicarbonate were added. The resulting reaction solution was heated under reflux for 4 h. The cooled reaction mixture was concentrated in vacuo, 100 ml of water were added, and the aqueous phase was extracted with ethyl acetate (4×60 ml). The combined organic phases were washed with saturated aqueous NaHCO3 solution, dried over magnesium sulfate and concentrated in vacuo. The residue was purified by chromatography on silica gel (mobile phase gradient 0-5% methanol in dichloromethane). Yield: 6.99 g (75%) of yellow solid

Workup

  1. customThe resulting reaction solution
  2. temperaturewas heated
  3. temperatureunder reflux for 4 h
  4. customThe cooled reaction mixture
  5. concentrationwas concentrated in vacuo, 100 ml of water
  6. additionwere added
  7. extractionthe aqueous phase was extracted with ethyl acetate (4×60 ml)
  8. washThe combined organic phases were washed with saturated aqueous NaHCO3 solution
  9. dry with materialdried over magnesium sulfate
  10. concentrationconcentrated in vacuo
  11. customThe residue was purified by chromatography on silica gel (mobile phase gradient 0-5% methanol in dichloromethane)

Sources & evidence

ORD record
ord-8edc9da634644482bce6e5668c9679bd
Source dataset
uspto-grants-2014_07
Patent number
US08791148B2

Reaction notes

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