Benzaldehyde → 4-Amino-1-Boc-piperidine

HRID 1978472Notes

Reaction equation

HRID 1978472 reaction equation
[NH2:1][CH:2]1[CH2:7][CH2:6][NH:5][CH2:4][CH2:3]1.[CH:8](=[O:15])C1C=CC=CC=1.[OH2:16].[C:17]1([CH3:23])[CH:22]=CC=C[CH:18]=1>>[NH2:1][CH:2]1[CH2:7][CH2:6][N:5]([C:8]([O:15][C:17]([CH3:23])([CH3:22])[CH3:18])=[O:16])[CH2:4][CH2:3]1

Participants

5

Reactant 4

HCID 240BenzaldehydeHCID 962WaterHCID 1140TolueneHCID 4243614-Piperidinamine

Product 1

HCID 12682914-Amino-1-Boc-piperidineYield 71%

Procedure

To a solution of 50 g (262.8 mM) of 4-amino-1-benzylpiperidine in 500 ml of methanol was added 5 g of 5% palladium-on-carbon (hydrous) and catalytic reduction was carried out at the hydrogen pressure of 5 kg/cm2 at 35° C. for 15 hours. The catalyst Pd/carbon was then filtered off and the filtrate was concentrated under reduced pressure to provide 4-aminopiperidine. To a solution of this 4-aminopiperidine in toluene (500 ml) was added 27.89 g (262.8 mM) of benzaldehyde and the mixture was refluxed for 3 hours, with the byproduct water being removed with a Dean-Stark trap. After cooling to room temperature, 63.08 g (289 mM) of di-tert-butyl dicarbonate was added dropwise gradually over about 1 hour and the mixture was stirred at room temperature overnight. After the solvent was distilled off under reduced pressure, 290 ml of 1N-aqueous solution of potassium hydrogen sulfate was added to the residue at room temperature and the mixture was stirred for 2 hours. The resulting crystal crop was harvested by filtration and rinsed with water, ethanol, and diethyl ether to provide tert-butyl 4-aminopiperidine-1-carboxylate ½ potassium hydrogen sulfate salt as colorless crystals (49.02 g, 71%).

Workup

  1. customremoved with a Dean-Stark trap
  2. addition63.08 g (289 mM) of di-tert-butyl dicarbonate was added dropwise gradually over about 1 hour
  3. distillationAfter the solvent was distilled off under reduced pressure, 290 ml of 1N-aqueous solution of potassium hydrogen sulfate
  4. additionwas added to the residue at room temperature
  5. stirringthe mixture was stirred for 2 hours
  6. filtrationThe resulting crystal crop was harvested by filtration
  7. washrinsed with water, ethanol, and diethyl ether

Sources & evidence

ORD record
ord-e21e1d9349454b46adf6328d8658c7a0
Source dataset
uspto-grants-2001_05
Patent number
US06235731B1

Reaction notes

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