An optimized synthesis of a key pharmaceutical intermediate methyl 4-[(1-oxopropyl)phenylamino]piperidine-4-carboxylate
| Autor: | Kiricojević Vesna D., Ivanović Milovan D., Mićović I.V., Đorđević J.B., Roglić Goran M., Došen-Mićović Ljiljana I. |
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| Jazyk: | angličtina |
| Rok vydání: | 2002 |
| Předmět: | |
| Zdroj: | Journal of the Serbian Chemical Society, Vol 67, Iss 12, Pp 793-802 (2002) |
| Druh dokumentu: | article |
| ISSN: | 0352-5139 1820-7421 |
| DOI: | 10.2298/JSC0212793K |
| Popis: | 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. |
| Databáze: | Directory of Open Access Journals |
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