Title: Synthesis of 2,5-substituted piperidines - transposition of 1,4-substitution pattern for the analgesic drug r6582
Authors: Baens, Np ×
Compernolle, Frans
Toppet, Suzanne
Hoornaert, Georges #
Issue Date: Jan-1993
Publisher: Pergamon-elsevier science ltd
Series Title: Tetrahedron vol:49 issue:15 pages:3193-3202
Abstract: This report describes the synthesis of cis 5-(1,3-dihydro-2-oxo-2H-benzimidazol-1-yl)-2-p-fluorophenyl-1-methylpiperidine (1a) and the analogous cis and trans 1-benzylpiperidines 2a,b. Key steps in the synthesis were the alpha-chlorination of the lactams 5 and 6 (1-methyl-and 1-benzyl-6-p-fluorophenyl-2-piperidinone), and nucleophilic substitution of the resulting cis and trans 3-chloro lactams 8a,b and 9a,b. H-1 NMR analysis for the epimeric 3,6-substituted lactam compounds revealed a preferred axial orientation for the 3-chloro substituent and an equatorial orientation for the 3-(oxobenzimidazolyl) group. For the reduced compound, cis N-methyl piperidine 1a, a conformational equilibrium was observed. This was shifted to the [2ax,5eq]form for the cis N-benzyl analogue 2a.
ISSN: 0040-4020
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Molecular Design and Synthesis
× corresponding author
# (joint) last author

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