63587-45-1Relevant academic research and scientific papers
Inexpensive multigram-scale synthesis of cyclic enamines and 3-N spirocyclopropyl systems
Kumar, Pratik,Zainul, Omar,Laughlin, Scott T.
supporting information, p. 652 - 656 (2018/02/07)
Cyclic enamines are important synthons for many synthetic and pharmacological targets. Here, we report an inexpensive, catalyst-free, multigram-scale synthesis for cyclic enamines with exocyclic double bonds and four- to seven-membered rings. This strategy is more conducive to scale up, permissive of functionalization around the cyclic system, and less sensitive to the nature of the N-protecting group than previously-described methods for cyclic enamine synthesis. Further, we explore application of these enamines to the synthesis of highly-strained spirocyclic 3N-cyclopropyl scaffolds.
β-Hydroxypiperidinecarboxylates: Additions to the chiral pool from bakers' yeast reductions of β-ketopiperidinecarboxylates
Knight, David W.,Lewis, Neil,Share, Andrew C.,Haigh, David
, p. 3673 - 3683 (2007/10/03)
Reduction of the piperidine keto esters 16-19 using fermenting bakers' yeast provides high yields of the corresponding hydroxy esters 20, 26, 32 and 37 respectively, exclusively as the cis-diastereoisomers and with good levels (≥80%) of enantiomeric enrichment. The relative stereochemistries of the products were deduced from NMR data while the absolute configurations were determined by degradation to known piperidinemethanol derivatives or, in the case of hydroxy ester 37, by homologation to (R)-3-quinuclidinol 41b.
Syntheses of piperidine and perhydroazepine derivatives, precursors of two selective antagonists of muscarinic M2 receptors: AF-DX 384 and its perhydroazepine isomer
Perrio-Huard, Cecile,Ducandas, Christophe,Lasne, Marie Claire,Moreau, Bernard
, p. 2925 - 2932 (2007/10/03)
Several routes to the synthesis of the polyamines 2a and 2b required for the preparation of the muscarinic antagonists AF-DX 384 1a and its perhydroazepine isomer 1b respectively have been developed and compared. Piperidine 2a has been obtained in 4 steps in 13-15% overall yield from 2-(chloromethyl)-pyridine 3. The perhydroazepine 2b has been prepared in 4 steps in 49% overall yield from 3-aminolactam 7. Transformations of piperidinemethanol 11 afford exclusively compound 2a (5 steps, 17-20% overall yield), via the N-tosylpiperidine 12, but lead to a 1:1 mixture of isomers 2a and 2b (4 steps, 15-20% overall yield for compounds 2a and 2b) via the N-(cyanomethyl)piperidine 15. Limitations to the ring enlargement of piperidine derivatives as a function of the heterocyclic nitrogen substituent are defined.
