170098-29-0Relevant articles and documents
Synthesis and characterization of all possible diastereoisomers of alvimopan
Reddy, Beeravalli Ramalinga,Dubey, Manoj Kumar,Ramana Reddy, Ch. Venkata,Bandichhor, Rakeshwar
, p. 963 - 972 (2018/05/28)
Isolation of all possible diastereomers of alvimopan 1 was found to be challenging. In order to perform cut off studies during analytical method development, it was mandatory to synthesize and characterize all the diastereomeric impurities. Here in, our efforts toward the synthesis and isolation of alvimopan (1) diastereomers are discussed.
Synthesis of trans-3,4-dimethyl-4-(3-hydroxyphenyl)piperidine opioid antagonists: Application of the cis-thermal elimination of carbonates to alkaloid synthesis
Werner, John A.,Cerbone, Louis R.,Frank, Scott A.,Ward, Jeffrey A.,Labib, Parviz,Tharp-Taylor, Roger W.,Ryan
, p. 587 - 597 (2007/10/03)
Improved syntheses of two trans-3,4-dimethyl-4-(3-hydroxyphenyl)piperidine opioid antagonists from 1,3-dimethyl-4-piperidinone are described. The 1,3-dimethyl-4-arylpiperidinol 23 was selectively dehydrated in a two step process to the 1,3-dimethyl-4-aryl-1,2,3,6-tetrahydropyridine 26 by the cis-thermal elimination of the corresponding alkyl carbonate derivative at 190°C. In the presence of a basic nitrogen, the success of the elimination was found to be critically dependent upon the nature of the carbonate alkyl group, with Et, i-Bu, and i-Pr being preferred (90% yield). Alkylation of the metalloenamine, formed by deprotonation of 26 with n-BuLi, proceeded regio- and stereospecifically to give the trans-3,4-dimethyl-4-aryl-1,2,3,4-tetrahydropyridine 27, which was converted in three steps to the common intermediate, (3R,4R)-3,4-dimethyl-4-(3-hydroxyphenyl)piperidine. LY255582, a centrally-active opioid antagonist, and LY246736-dihydrate, a peripherally-active opioid antagonist, were prepared from 1,3-dimethyl-4-piperidinone in 11.8% yield (8 steps) and 6.2% yield (12 steps), respectively.
