Azabicycloalkanes as analgetics. II. An improved synthesis of 1-phenyl-6-azabicyclo(3,2,1)octane derivatives

Autor:	Seiichi Saito, Masatoshi Kawamori, Yasushi Honma, H. Inoue, Mikio Takeda, Katsuyuki Noguchi, Goro Tsukamoto, Yasuhiko Yamawaki
Rok vydání:	1976
Předmět:	chemistry.chemical_classification Ketone Bicyclic molecule Grignard reaction General Chemistry General Medicine Reductive amination chemistry.chemical_compound chemistry Bromide Drug Discovery Lactam Hydrocyanation Organic chemistry Octane
Zdroj:	Chemical and Pharmaceutical Bulletin. 24:1514-1526
ISSN:	1347-5223 0009-2363
DOI:	10.1248/cpb.24.1514
Popis:	An improved synthesis of 6, 7endo-dimethyl-1-(3-hydroxyphenyl)-6-azabicyclo [3, 2, 1]-octane (10c), a new analgetic agent with a low addiction liability, is described. Grignard reaction of 3-ethoxy-2-cyclohexen-1-one (1) with m-methoxyphenylmagnesium bromide gave the α, β-unsaturated ketone (2b). Hydrocyanation of the latter followed by methanolysis yielded the keto ester (5b). The bicyclic lactam (8b), a key intermediate in the original synthesis was obtained by reductive amination of 5b with methylamine. As a result of this sequence of reactions, 10c could be obtained in 7 steps from 1 in 42% overall yield. By an application of this new method, a number of 1-phenyl-6-azabicyclo [3, 2, 1] octane derivatives with various substituents on benzene ring (10d-k), nitrogen (31), and C8 (39-46) have been prepared for pharmacological evaluation.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::2fd758e73dd228c276ce873d84efda61 https://doi.org/10.1248/cpb.24.1514 Zobrazit plný text záznamu