277744-08-8Relevant academic research and scientific papers
Synthesis of Enantiopure trans-3,4-Disubstituted Piperidines. An Enantiodivergent Synthesis of (+)- And (-)-Paroxetine
Amat, Mercedes,Bosch, Joan,Hidalgo, Jose,Canto, Margalida,Perez, Maria,Llor, Nuria,Molins, Elies,Miravitlles, Carles,Orozco, Modesto,Luque, Javier
, p. 3074 - 3084 (2007/10/03)
Reaction of (R)-phenylglycinol with methyl 5-oxopentanoate gave either bicyclic lactam cis-1 (the kinetic product) or its isomer trans-1 (under equilibrating conditions) as the major products, which were converted to the corresponding (cis or trans) unsaturated lactams 4 and 5. On treatment with lithium alkyl (or aryl) cyanocuprates, these chiral building blocks undergo conjugate addition to give enantiopure trans-3,4-substituted 2-piperidone derivatives in high yield and stereoselectivity. The synthetic potential of this transformation is illustrated by the synthesis of (+)-femoxetine and the two enantiomers of the known antidepressant paroxetine.
