159153-38-5

Upstream product

• 86953-79-9 tert-butyl pyrrolidine-1-carboxylate 

Downstream Products

• 154344-51-1 2,5-bis(trimethylsilyl)-N-benzylpyrrolidine 

Relevant academic research and scientific papers

Synthesis and analgesic activity of hydrochlorides and quaternary ammoniums of epibatidine incorporated with amino acid ester

Hydrochloride derivatives 5a-c and quaternary ammonium derivatives 6a-c of epibatidine incorporated with amino acid ester were synthesized and evaluated for their in vivo analgesic activity and toxicity. Among all tested compounds, compound 6c has the most potent analgesic activity. The quaternary ammonium salts 6a and 6c showed better analgesic activity than the corresponding hydrochlorides 5a and 5c. Both 5a-c and 6a-c showed significantly lower toxicity than epibatidine itself.

Stereoselective construction of X-azabicyclo[m.2.1]alkanes by [3+2]-cycloaddition of non-stabilized cyclic azomethine ylides: Synthesis of enantiopure constrained amino acids and formal total synthesis of optically active epibatidine

A new and general strategy for the stereoselective construction of X-azabicyclo[m.2.1]alkanes has been developed by the [3+2]-cycloaddition of cyclic azomethine ylides with suitable achiral dipolarophiles. The cyclic azomethine ylides, where the whole of the ylide conjugation is in the ring, have been generated by the sequential double desilylation of the N-alkyl-α,α′-bis(trimethylsilyl) cyclic amines utilizing Ag(I)F as one electron oxidant. The structural rigidity of cyclic azomethine ylides has allowed preferential facial discrimination by the dipolarophile resulting into very good exolendo selectivity. The exolendo selectivity associated with these cycloadditions has been further exploited to access optically pure X-azabicyclo[m.2.1]alkanes by carrying out the cycloadditions with the Oppolzer's acryloyl dipolarophile. Application of this methodology is demonstrated by the construction of few constrained amino acids related to azabicyclic structural framework and the formal total synthesis of optically active epibatidine.

[3+2]-Cycloaddition of nonstabilized azomethine ylides, Part 9: A general approach for the construction of X-azabicyclo[m.2.1]alkanes in optically pure form by asymmetric 1,3-dipolar cycloaddition reactions

A general strategy for the construction of X-azabicyclo[m.2.1]alkane frameworks in optically pure form is reported by the asymmetric [3+2]- cycloaddition reaction of cyclic azomethine ylides with Oppolzer's acryloyl camphor sultam.

[3 + 2] Cycloaddition of nonstabilized azomethine ylides. 7. Stereoselective synthesis of epibatidine and analogues

Epibatidine (1) is synthesized by employing a [3 + 2] cycloaddition strategy as a key step via nonstabilized azomethine ylide 10, generated by one-electron oxidative double desilylation of N-benzyl-2,5- bis(trimethylsilyl)pyrrolidine (12). Cycloaddition of 10 with trans-ethyl-3- (6-chloro-3-pyridyl)-2-propenoate (22a) gives 26 in which the 6-chloro-3- pyridyl moiety is endo-oriented. Decarboxylation followed by debenzylation gives unnatural epimer 30 of 1. The required cycloadduct 33, in which 6- chloro-3-pyridyl moiety is exo-oriented, is obtained stereoselectively utilizing cis-ethyl-(6-chloro-3-pyridyl)-2-propenoate (22b) as dipolarophile. 30 is also converted to 1 by epimerization reaction using KO(t)Bu. An alternative route involving conjugate addition of 6-chloro-3-iodo pyridine (37) to 36, obtained by cycloaddition of 10 with ethyl propiolate, is also suggested for the stereoselective synthesis of 1. A number of substituted epibatidines (38, 39, 40, 41, and 42) are synthesized through this strategy using appropriate dipolarophiles. Formal synthesis of the N-methyl homoepibatidine 48 and its epimer 46 is suggested from the cycloaddition of homologous azomethine ylide 44, derived from 43, with 22a and 22b, respectively.

An Expeditious Synthesis of Epibatidine and Analogues

An efficient synthesis of Epibatidine and its analogues via cycloaddition of non-stabilised azomethine ylide and substituted 6-chloro-3-vinyl pyridine.