Malonic Acid → [4-Amino-1-(tert-butoxycarbonyl)piperidin-4-yl]acetic acid

HRID 1481102Notes

Reaction equation

HRID 1481102 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11](=O)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:15]([OH:21])(=[O:20])[CH2:16]C(O)=O.C([O-])(=O)C.[NH4+:26]>CCCCO>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]([NH2:26])([CH2:16][C:15]([OH:21])=[O:20])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 867Malonic AcidHCID 517165Ammonium AcetateHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylate

Product 1

HCID 49759554[4-Amino-1-(tert-butoxycarbonyl)piperidin-4-yl]acetic acidYield 36%

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Procedure

A mixture of 4-oxo-piperidine-1-carboxylic acid tert-butyl ester (3.5 g, 17.55 mmol) (Sigma-Aldrich), malonic acid (2.0 g, 19.30 mmol) and ammonium acetate (3.1 g, 40.36 mmol) in n-BuOH was refluxed for 3 h. After cooled, white solid was collected, rinsed with EtOAc and dried in vacuo to provide the title compound 1.61 g (6.2 mmol) in 36% yield. 1H NMR (200 MHz) in D2O, δ ppm: 3.66 (br m, 2H), 3.10 (br m, 2H), 2.45 (s, 2H), 1.69 (br m, 4H), 1.28 (s, 9H).

Workup

  1. temperaturewas refluxed for 3 h
  2. temperatureAfter cooled
  3. customwhite solid was collected
  4. washrinsed with EtOAc
  5. customdried in vacuo

Sources & evidence

ORD record
ord-447fa037673941eb9c7303a6d34ec54c
Source dataset
uspto-grants-2016_08
Patent number
US09409892B2

Reaction notes

Loading…