A New Practical Route for the Manufacture of (4aR,10aR)-9-Methoxy-1-methyl-6-trimethylsilanyl- 1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinoline

Autor:	Ernst Küsters, J. Nozulak, Markus Bänziger, Luigi La Vecchia, Wolfgang Marterer
Rok vydání:	2003
Předmět:	chemistry.chemical_compound chemistry Yield (chemistry) Organic Chemistry Quinoline Organic chemistry Physical and Theoretical Chemistry Enantiomer Derivative (chemistry)
Zdroj:	Organic Process Research & Development. 7:904-912
ISSN:	1520-586X 1083-6160
DOI:	10.1021/op034112x
Popis:	Different synthetic routes to the enantiomerically pure octahydrobenzo[g]quinoline derivative JNZ092 were evaluated for their suitability to rapidly prepare a first clinical batch on a kilogram scale. On the basis of the experience of previous octahydrobenzo[g]quinoline projects a new linear synthesis of JNZ092 was established and scaled up successfully. The overall yield was increased by a factor 10 and the preparation time shortened significantly as compared to those of the medicinal chemistry route. As the key strategy all atoms of the octahydrobenzo[g]quinoline skeleton were introduced early by the reaction of the 6-lithiated 1,7-dimethoxynaphthalene with ethyl-2-cyano-3-ethoxyacrylate. As a valuable technological refinement the practicability of a chromatographic technique with repetitive feed injection for the problematic separation of the enantiomers was demonstrated.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::b1fc6db0b2c5e8f3f17728465f44f092 https://doi.org/10.1021/op034112x Zobrazit plný text záznamu