1370650-93-3Relevant academic research and scientific papers
Asymmetric syntheses of 3,4-syn- and 3,4-anti-3-substituted-4- aminopiperidin-2-ones: Application to the asymmetric synthesis of (+)-(3S,4R)-cisapride
Davies, Stephen G.,Huckvale, Rosemary,Lee, James A.,Lorkin, Thomas J.A.,Roberts, Paul M.,Thomson, James E.
, p. 3263 - 3275 (2012/06/01)
The conjugate addition of lithium (R)-N-benzyl-N-(α-methylbenzyl) amide to δ-(N-allylamino)-α,β-unsaturated esters, followed by N-deallylation and cyclisation of the resultant β,δ-diamino esters, gives the corresponding 4-aminopiperidin-2-ones as single diastereoisomers (>99:1 dr). Subsequent deprotonation with LiHMDS and functionalisation of the resultant lithium enolate gives 3,4-anti-3-substituted-4-aminopiperidin-2-ones in >99:1 dr. Alternatively, in situ oxidation of the intermediate lithium (Z)-β-amino enolates formed upon conjugate addition gives α-hydroxy-β,δ-diamino esters, which after N-deallylation and cyclisation gives the corresponding 3,4-syn-3-hydroxy-4-aminopiperidin-2-ones in >99:1 dr. The utility of this methodology was successfully demonstrated in a concise asymmetric synthesis of the gastroprokinetic agent (+)-(3S,4R)- cisapride {(+)-(3S,4R)-N(1)-[3′-(4″-fluorophenoxy)propyl]-3-methoxy- 4-(2?-methoxy-4?-amino-5?-chlorobenzamido)piperidine} in nine steps from commercially available starting materials with an overall yield of 19%.
