A new entry into cis-3-amino-2-methylpyrrolidines via ring expansion of 2-(2-hydroxyethyl)-3-methylaziridines.
3-Amino-2-methylpyrrolidines were prepared via a novel protocol, involving the reductive ring closure and O-deprotection of gamma-acetoxy-alpha-chloroketimines towards 2-(2-hydroxyethyl)-3-methylaziridines, followed by ring expansion of the latter into 3-bromopyrrolidines via intermediate bicyclic aziridinium salts and consecutive nucleophilic displacement of the bromo atom by azide towards 3-azidopyrrolidines. A final reduction of the azide moiety furnished 3-amino-2-methylpyrrolidines in high yields. Thus, a new formal synthesis of the antipsychotic emonapride was developed through preparation and further aroylation of cis-3-amino-1-benzyl-2-methylpyrrolidine.
D'hooghe
Matthias
M
Department of Organic Chemistry, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, B-9000, Ghent, Belgium.
Aelterman
Wim
W
De Kimpe
Norbert
N
D014150:Antipsychotic Agents / Q000138:chemical synthesis* / Q000737:chemistry; D001388:Aziridines / Q000138:chemical synthesis* / Q000737:chemistry*; D001549:Benzamides / Q000138:chemical synthesis* / Q000737:chemistry; D002625:Chemistry, Organic / Q000379:methods*; D002626:Chemistry, Pharmaceutical / Q000379:methods; D015195:Drug Design; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D008968:Molecular Conformation; D015394:Molecular Structure; D011759:Pyrrolidines / Q000737:chemistry*; D013237:Stereoisomerism
D014150:Antipsychotic Agents; D001388:Aziridines; D001549:Benzamides; D011759:Pyrrolidines; C030265:nemonapride