Title of article :
A New Synthetic Approach to 1-[(3R,4R)-1-Cyclooctylmethyl-3-hydroxymethyl-4-piperidyl]-3-ethyl-1,3-dihydro-benzimidazol-2-one (J-113397), the first non-peptide ORL-1 receptor antagonist Original Research Article
Carmela De Risi، نويسنده , , Gian Piero Pollini، نويسنده , , Claudio Trapella، نويسنده , , Ilaria Peretto، نويسنده , , Silvano Ronzoni، نويسنده , , Giuseppe A.M. Giardina، نويسنده ,
Issue Information :
روزنامه با شماره پیاپی سال 2001
An efficient approach to 1-[(3R,4R)-1-cyclooctylmethyl-3-hydroxymethyl-4-piperidyl]-3-ethyl-1,3-dihydro-benzimidazol-2-one (J-113397) , the first non-peptide ORL-1 receptor antagonist described in literature, is outlined. After construction of the piperidine framework through Dieckmann cyclization of the Michael adduct of cyclooctylmethylamine to methyl acrylate, condensation with o-phenylendiamine produced the β-enamino ester , which has been conveniently used to construct the benzimidazolone substituent at C-4. Catalytic hydrogenation of intermediate followed by base-promoted cis–trans isomerization of the key compound led to the formation of ester , which was converted to the racemic title compound by LiAlH4 reduction. The pure enantiomers were obtained by chiral preparative HPLC separation using a derivatized cellulose-based stationary phase.
Journal title :
Bioorganic and Medicinal Chemistry