Hydrochloric Acid → 4-(Piperidin-4-yl)butanoic acid
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]1Participants
4
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.