- A short synthesis of cisapride: A gastrointestinal stimulant derived from cis-4-amino-3-methoxypiperidine
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Cisapride was synthesized in seven steps from piperidin-4-one by using a diastereoselective reduction of an α-oximino ether with the complex BH3·THF.
- Cossy, Janine,Molina, Jose L,Desmurs, Jean-Roger
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- 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
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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%.
- Davies, Stephen G.,Huckvale, Rosemary,Lee, James A.,Lorkin, Thomas J.A.,Roberts, Paul M.,Thomson, James E.
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p. 3263 - 3275
(2012/06/01)
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- Concise, efficient and highly selective asymmetric synthesis of (+)-(3S,4R)-cisapride
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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} from commercially available starting materials has been developed. The key step of this synthesis employs the diastereoselective conjugate addition of lithium (R)-N-benzyl-N-(α- methylbenzyl)amide to tert-butyl 5-[N-3′-(4″-fluorophenoxy)propyl-N- allylamino]pent-2-enoate and in situ enolate oxidation with (-)- camphorsulfonyloxaziridine to set the (3S,4R)-configuration found within the piperidine ring of the product. This synthesis proceeds in 9 steps from commercially available 1-(4′-fluorophenoxy)-3-bromopropane with an overall yield of 19%.
- Davies, Stephen G.,Huckvale, Rosemary,Lorkin, Thomas J.A.,Roberts, Paul M.,Thomson, James E.
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p. 1591 - 1593
(2011/12/14)
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- Benzotriazol-1-yl alkyl carbonate, a new convenient and inexpensive coupling agent to prepare an active ester for the synthesis of amide
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Benzotriazol-1-yl alkyl carbonate 1 has been found to be a new convenient and inexpensive coupling agent to prepare an active ester 2 for the synthesis of an amide 3 in good yield and with high purity.
- Lee, Jin Soo,Oh, Yoon Seok,Lim, Jae Kyung,Yang, Wang Yong,Kim, Ik Hoe,Lee, Chi Woo,Chung, Yong Ho,Yoon, Sung June
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p. 2547 - 2557
(2007/10/03)
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