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Optimizovana sinteza značajnog farmaceutskog intermedijera metil 4-[(1-oksopropil)fenilamino]piperidin-4-karboksilata

dc.creatorKiricojević, Vesna
dc.creatorIvanović, Milovan D.
dc.creatorMićović, Ivan
dc.creatorĐorđević, Jelena B.
dc.creatorRoglić, Goran
dc.creatorDošen-Mićović, Ljiljana
dc.date.accessioned2019-04-24T14:44:29Z
dc.date.available2019-04-24T14:44:29Z
dc.date.issued2002
dc.identifier.issn0352-5139
dc.identifier.urihttp://cer.ihtm.bg.ac.rs/handle/123456789/2677
dc.description.abstractAn efficient synthesis of methyl 4-[(1-oxopropyl)phenylamino]piperidine-4-carboxylate (7) has been developed, starting from 1-benzylpiperidin-4-one (1), The compound is a key intermediate in the synthesis of new generation, highly active narcotic analgesics, such as remifentanil. as well as the novel classes of fentanyl analogues, An optimized Strecker-type condensation of piperidone 1 with aniline and HCN yielded the anilino-nitrile 2 (approximate to90%) which, upon selective hydrolysis with cone. H2SO4, gave the anilino-amide 3. After vigorous basic hydrolysis of 3, followed by acidification and successive treatment with SOCl2 and MeOH, the anilino-ester 5 was obtained (40-45%, in 3 steps). N-Acylation of 5 with propionyl chloride yielded the anilido-ester 6 (70-80%). In the final step, the catalytic N-debenzylation of 6 was examined under various conditions and optimized to yield 7 in near quantitative yields.en
dc.description.abstractU ovom radu razvijena je efikasna sinteza metil 4-[(1-oksopropil)fenilamino]piperidin-4-karboksilata (7), prolazeći od 1-benzil piperidin-4-on-1 (1). Jedinjenje 7 je ključni intermedijer u sintezi nove generacije visoko aktivnih narkotičkih analgetika, kao što je remifentanil a takođe i novih klasa analoga fentanyla. U optimizovanoj Strecker-ovoj kondenzaciji priperidona 1 sa anilinom i HCN, dobijen je anilino-nitril 2 (≈90%) prinos čijom je selektivnom hidrolizom pomoću konc. H2SO4 postao anilino-amid 3. Intenzivnom baznom hidrolizom ovog intermedijera, zakišeljavanjem a zatim sukcesivno reakcijom sa SOCl2 i MeOH sintetisan je anilino-estar 5 (≈40–45% prinos u 3 faze). N-acelovanjem anilino-estra 5 sa propionil hloridom postao je anilido-estar 6 (≈70–80% prinos). U poslednjom fazi sinteze izvršena je optimizacija katalitičkog N-debenzilovanja anilido-estra 6 do finalnog proizvoda 7, u približno kvantitativnom prinosu.sr
dc.publisherSerbian Chemical Soc, Belgrade
dc.rightsopenAccess
dc.sourceJournal of the Serbian Chemical Society
dc.subjectoptimized Strecker reactionen
dc.subjectfunctionalized piperidinesen
dc.subjectfunctionalized piperidinesen
dc.subjectfentanyl-type central analgesicsen
dc.subjectfentanyl-type central analgesicsen
dc.titleAn optimized synthesis of a key pharmaceutical intermediate methyl 4-[(1-oxopropyl)phenylamino]piperidine-4-carboxylateen
dc.titleOptimizovana sinteza značajnog farmaceutskog intermedijera metil 4-[(1-oksopropil)fenilamino]piperidin-4-karboksilatasr
dc.typearticle
dc.rights.licenseBY-NC-ND
dcterms.abstractДосен-Мицовиц, Л; Дјордјевиц, Ј. Б.; Мицовиц, Иван; Кирицојевиц, В. Д.; Ивановић, Милован; Роглић, Горан; Оптимизована синтеза значајног фармацеутског интермедијера метил 4-[(1-оксопропил)фениламино]пиперидин-4-карбоксилата; Оптимизована синтеза значајног фармацеутског интермедијера метил 4-[(1-оксопропил)фениламино]пиперидин-4-карбоксилата;
dc.citation.volume67
dc.citation.issue12
dc.citation.spage793
dc.citation.epage802
dc.citation.other67(12): 793-802
dc.citation.rankM23
dc.identifier.doi10.2298/JSC0212793K
dc.identifier.fulltexthttp://cer.ihtm.bg.ac.rs//bitstream/id/8933/2704.pdf
dc.identifier.scopus2-s2.0-0036989655
dc.identifier.wos000180192500001
dc.type.versionpublishedVersion


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