Benzaldehyde → 4-Aminomethyl-1-N-Cbz-piperidine

HRID 1934808Notes

Reaction equation

HRID 1934808 reaction equation
[NH2:1][CH2:2][CH:3]1[CH2:8][CH2:7][NH:6][CH2:5][CH2:4]1.C(=O)C1C=CC=CC=1.Cl[C:18]([O:20][CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)=[O:19].OS([O-])(=O)=O.[K+]>C1(C)C=CC=CC=1>[CH2:21]([O:20][C:18]([N:6]1[CH2:7][CH2:8][CH:3]([CH2:2][NH2:1])[CH2:4][CH2:5]1)=[O:19])[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1

Participants

6

Reactant 4

HCID 240BenzaldehydeHCID 10387Benzyl chloroformateHCID 235274-(Aminomethyl)piperidineHCID 516920Potassium bisulfate

Product 1

HCID 219554994-Aminomethyl-1-N-Cbz-piperidineYield 91%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
0 °C

Procedure

22.2 g(0.2 mol) of 4-aminomethyl piperidine was dissolved in 250 ml of toluene and 21.2 g(0.2 mol) of benzaldehyde was added thereto. The reaction mixture was heated to reflux for 3 hours with Dean-stack and then cooled down to 0° C. 34.2 g(0.2 mol) of benzyl chloroformate was added dropwise while stirring. The reactants were stirred for 3 hours and 220 ml of 1N KHSO4 was added at room temperature. The reaction solution was extracted with 200 ml of diethylether 3 times and the aqueous layer was basified with sodium hydroxide. After the aqueous solution was treated with saturated sodium chloride solution, it was extracted with 100 ml of dichloromethane 3 times. and the organic layer was dried over magnesium sulfate. Removal of dichloromethane under reduced pressure provided 38 g of the title compound(Yield 91%, MW 248).

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux for 3 hours with Dean-stack
  3. stirringThe reactants were stirred for 3 hours
  4. extractionThe reaction solution was extracted with 200 ml of diethylether 3 times
  5. additionAfter the aqueous solution was treated with saturated sodium chloride solution, it
  6. extractionwas extracted with 100 ml of dichloromethane 3 times
  7. dry with materialand the organic layer was dried over magnesium sulfate
  8. customRemoval of dichloromethane under reduced pressure

Sources & evidence

ORD record
ord-f041004e8b964a98adf7814c4e1bb951
Source dataset
uspto-grants-2002_05
Patent number
US06384061B1

Reaction notes

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