Hydrochloric Acid → 4-(Piperidin-4-yl)butanoic acid

HRID 568108Notes

Reaction equation

HRID 568108 reaction equation
C([O:3][C:4](=[O:19])[CH:5]([CH2:11][CH2:12][C:13]1[CH:18]=[CH:17][N:16]=[CH:15][CH:14]=1)C(OCC)=O)C.Cl.N1C=CC(CCCC(O)=O)=CC=1>>[NH:16]1[CH2:17][CH2:18][CH:13]([CH2:12][CH2:11][CH2:5][C:4]([OH:19])=[O:3])[CH2:14][CH2:15]1

Participants

4

Reactant 3

HCID 313Hydrochloric AcidHCID 2801722Diethyl 2-[2-(4-pyridyl)ethyl]malonateHCID 31596254-Pyridinebutanoic acid

Product 1

HCID 51677024-(Piperidin-4-yl)butanoic acid

Procedure

In an especially preferred preparation of VIII, 2-(4-pyridyl)ethylmalonic acid diethyl ester is taken up in aqueous acid, preferably aqueous HCl, and decarboxylated by heating at reflux. A catalyst as described above is then added to the resulting solution of 4-(4-pyridyl)butanoic acid XIII and the mixture is catalytically hydrogenated to give an aqueous solution of 4-(4-piperidyl)butanoic acid XIV. The catalyst is then filtered off, the acidic solution of XIV is made basic with aqueous alkoxide and the benzyloxycarbonyl protecting group is introduced as described above. The 1-[(phenylmethoxy)carbonyl]-4-piperidinebutanoic acid is then extracted into an organic solvent and condensed with N-ethylglycine as described above to give VIII.

Workup

  1. temperaturedecarboxylated by heating
  2. temperatureat reflux

Sources & evidence

ORD record
ord-be3279bcadb540008d49559487d58a5f
Source dataset
uspto-grants-2001_01
Patent number
US06180759B2

Reaction notes

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