Pethidine Synthesis
3
Pethidine N O O Ethyl 1-methyl-4-phenylpiperidine-4-carboxylate Meperidine Pethidine HCl • Roche (manufacturer) o Tablets, injection
Transcript of Pethidine Synthesis
Pethidine
NO
O Ethyl 1-methyl-4-phenylpiperidine-4-carboxylate Meperidine Pethidine HCl
• Roche (manufacturer) o Tablets, injection
Pethidine synthesis
N
pethidine
O
O
OH
HN
OH
diethanolamine
Br OH
N
OH
Cl
N
Cl
CN
Na+NH2−
sodium amide
benzyl cyanide
Cl
N
Cl
H
CN−
−NaCl
−NH3
Cl
N
CNNH2 Na+−H
Cl
N
CN−−NaCl N
CN
NNC
aq. H2SO4
NHOOC
EtOH
HCl(g)N
O
O
H2, Pd/C
NHO
O
CH3I, Et3N
Remington, 20th Edition, 2000, 1448
pethidine HClm.p. 186-189oC
COCl2
A number of pethidine-type analogues have been synthesized and are used as antidiarrhoeal agents – loperamide and diphenoxylate.
Pethidine metabolism Pethidine has a relatively short duration of action due to efficient inactivation by ester hydrolysis to the corresponding acid. A fraction of the dose is also metaboised by oxidative N-dealkylation, affording norpethidine which has been implicated in CNS toxicity. Both metabolited form a common nor acid which is conjugated and eliminated.
N
pethidine
O
O
NHO
O
NHO
O
NHHO
O
esterase(major)
minorconjugation
