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An optimized synthesis of a key pharmaceutical intermediate methyl 4-[(1-oxopropyl)phenylamino]piperidine-4-carboxylate
Optimizovana sinteza značajnog farmaceutskog intermedijera metil 4-[(1-oksopropil)fenilamino]piperidin-4-karboksilata
dc.creator | Kiricojević, Vesna D. | |
dc.creator | Ivanović, Milovan D. | |
dc.creator | Mićović, I.V. | |
dc.creator | Popović-Djordjević, Jelena | |
dc.creator | Roglić, Goran M. | |
dc.creator | Došen-Mićović, Ljiljana I. | |
dc.date.accessioned | 2020-12-17T18:00:16Z | |
dc.date.available | 2020-12-17T18:00:16Z | |
dc.date.issued | 2002 | |
dc.identifier.issn | 0352-5139 | |
dc.identifier.uri | http://aspace.agrif.bg.ac.rs/handle/123456789/493 | |
dc.description.abstract | An 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 remifintanil, 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(≈90%) which, upon selective hydrolysis with conc. 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.abstract | U 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.publisher | Srpsko hemijsko društvo, Beograd | |
dc.rights | openAccess | |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/4.0/ | |
dc.source | JOURNAL OF THE SERBIAN CHEMICAL SOCIETY | |
dc.subject | optimized Strecker reaction | en |
dc.subject | functionalized piperidines | en |
dc.subject | fentanyl-type central analgesics | en |
dc.title | An optimized synthesis of a key pharmaceutical intermediate methyl 4-[(1-oxopropyl)phenylamino]piperidine-4-carboxylate | en |
dc.title | Optimizovana sinteza značajnog farmaceutskog intermedijera metil 4-[(1-oksopropil)fenilamino]piperidin-4-karboksilata | sr |
dc.type | article | |
dc.rights.license | BY-NC-ND | |
dc.citation.epage | 802 | |
dc.citation.issue | 12 | |
dc.citation.other | 67(12): 793-802 | |
dc.citation.rank | M23 | |
dc.citation.spage | 793 | |
dc.citation.volume | 67 | |
dc.identifier.doi | 10.2298/JSC0212793K | |
dc.identifier.fulltext | http://aspace.agrif.bg.ac.rs/bitstream/id/3426/490.pdf | |
dc.identifier.scopus | 2-s2.0-0036989655 | |
dc.identifier.wos | 000180192500001 | |
dc.type.version | publishedVersion |