277743-97-2

Upstream product

• 24424-99-5 di-tert-butyl dicarbonate 
• 872544-55-3 rel-[(3R,4S)-4-phenylpiperidin-3-yl]methanol 
• 277743-71-2 (3R,6R,7S,8aS)-6-(methoxycarbonyl)-5-oxo-3,7-diphenyl-2,3,6,7,8,8a-hexahydro-5H-oxazolo[3,2-a]pyridine 
• 182957-46-6 (3R,8aS)-6-(methoxycarbonyl)-5-oxo-3-phenyl-2,3,8,8a-tetrahydro-5H-oxazolo[3,2-a]pyridine 
• 277743-59-6 (3R,8aS)-6-(benzyloxycarbonyl)-5-oxo-3-phenyl-6-(phenylselanyl)-2,3,6,7,8,8a-hexahydro-5H-oxazolo[3,2-a]pyridine 
• 152555-02-7 (3R,8aR)-5-oxo-3-phenyl-2,3,6,7,8,8a-hexahydro-5H-oxazolo[3,2-a]pyridine 
• 152615-80-0 (3R,8aS)-5-oxo-3-phenyl-2,3,6,7,8,8a-hexahydro-5H-oxazolo<3,2-a>pyridine 
• 14273-92-8 methyl 5-hydroxypentanoate 
• 6026-86-4 methyl 4-formylbutanoate 
• 872544-53-1 (R)-4-Phenyl-1,4,5,6-tetrahydro-pyridine-3-carboxylic acid methyl ester 
• 872544-52-0 (R)-4-Phenyl-1,4-dihydro-pyridine-3-carboxylic acid methyl ester 

Downstream Products

• 59859-58-4 femoxetine 
• 277744-02-2 (3R,4S)-1-(tert-butoxycarbonyl)-3-(p-methoxyphenoxymethyl)-4-phenylpiperidine 
• 277743-99-4 (3R,4S)-3-Methanesulfonyloxymethyl-4-phenyl-piperidine-1-carboxylic acid tert-butyl ester 

Relevant academic research and scientific papers

A new route to 3,4-disubstituted piperidines: Formal synthesis of (-)-paroxetine and (+)-femoxetine

A new route to 3,4-disubstituted piperidines was developed using chiral 1,4-dihydropyridines as key intermediates, the synthetic utility of which was demonstrated by formal synthesis of (-)-paroxetine and (+)-femoxetine.

Synthesis of Enantiopure trans-3,4-Disubstituted Piperidines. An Enantiodivergent Synthesis of (+)- And (-)-Paroxetine

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.