401502-00-9Relevant academic research and scientific papers
Concise, efficient and highly selective asymmetric synthesis of (+)-(3S,4R)-cisapride
Davies, Stephen G.,Huckvale, Rosemary,Lorkin, Thomas J.A.,Roberts, Paul M.,Thomson, James E.
, p. 1591 - 1593 (2011)
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%.
Alkyl trimethyl tin compounds as well as preparation method and application thereof
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Paragraph 0090-0092, (2021/06/22)
The invention discloses a series of alkyl trimethyl tin compounds as well as a preparation method and application thereof. The method comprises the following steps: uniformly mixing alkyl iodide, alkali and hexamethylditin in a solvent, reacting at 30 DEG C for 24 hours, and concentrating after the reaction is finished; and then carrying out column chromatography to obtain a pure alkyl trimethyl tin product. The raw material adopted by the invention is the alkyl iodide which is an important supplement compared with the existing reaction method adopting alkyl halide and Grignard reagent as raw materials, and the method has the advantages of wide raw material source, cheap and easily available raw materials, low production cost, reaction at room temperature and no use of a transition metal catalyst. The reaction involved in the method has good tolerance and universality on functional groups, and substituent groups on alkyl can be hydrogen, methyl, tertiary butyl, fluorine, chlorine, bromine, cyano, trifluoromethyl, methoxyl, methylsulfonyl or ethyl ester group and the like.
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.
experimental part, 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%.
