Modification of 1-Substituents in the 2-Azabicyclo[2.1.1]hexane Ring System; Approaches to Potential Nicotinic Acetylcholine Receptor Ligands from 2,4-Methanoproline Derivatives

Journal of Organic Chemistry

Volumn 68, Issue 24, 2003, Pages 9348-9355

  Malpass, John R ^a   Patel, Anup B ^a   Davies, John W ^a   Fulford, Sarah Y ^a  

^a UNIVERSITY OF LEICESTER   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

NUCLEOPHILIC ATTACK;

AMINO ACIDS; CHEMICAL ACTIVATION; CHEMICAL MODIFICATION; PHOSPHOLIPIDS; SUBSTITUTION REACTIONS;

AROMATIC COMPOUNDS;

2 AZABICYCLO[2.1.1]HEXANE; 3 OXA 5 AZATRICYCLO[5.1.1.0 1.5]NONAN 4 ONE; CARBAMIC ACID DERIVATIVE; CARBENE; HEXANE; NICOTINIC RECEPTOR; PROLINE DERIVATIVE; UNCLASSIFIED DRUG;

ARTICLE; CHEMICAL MODIFICATION; DECARBOXYLATION; RING OPENING; SUBSTITUTION REACTION;

AZA COMPOUNDS; BICYCLO COMPOUNDS, HETEROCYCLIC; LIGANDS; MODELS, CHEMICAL; MOLECULAR STRUCTURE; NICOTINIC AGONISTS; PROLINE; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 0345686456     PISSN: 00223263     EISSN: None     Source Type: Journal    
DOI: 10.1021/jo035199n     Document Type: Article

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41. 3a.6
42. For typical procedures, see ref 12c. For the preparation of 20 we used potassium tert-butoxide in place of LDA.
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44. The purity of 20 was estimated to be greater than 90% by NMR. The spectra were complicated further owing to the presence not only of cis/trans isomers but also of slow rotation about the C-N bond. Spectra of many N-alkoxycarbonylamines in this work showed the effects of slow rotation (cf. ref 11).
45. Cox, C. D. PhD Thesis, University of Leicester, 2000. We thank Caroline Cox for a synthesis of 18b and the corresponding iodo-derivative. Details of coupling investigations will be reported in due course. We also acknowledge her additional assistance with the optimization of yields for compounds 2, 3a, and 4a.