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Asymmetric Synthesis. 39. Synthesis of 2-(1-Aminoalkyl)piperidines via 2-Cyano-6-phenyl Oxazolopiperidine
journal contributionposted on 1996-09-20, 00:00 authored by Olivier Froelich, Patrice Desos, Martine Bonin, Jean-Charles Quirion, Henri-Philippe Husson, Jieping Zhu
The asymmetric synthesis of a series of 2-(1-aminoalkyl) piperidines using (−)-2-cyano-6-phenyloxazolopiperidine 1 is described. LiAlH4 reduction of 1 followed by hydrogenolysis led to the diamine 3. The same strategy applied to C-2-methylated compound 7 afforded [(2S)-2-methylpiperidin-2-yl]methanamine (9). Addition of lithium derivatives to the cyano group of 1 resulted in the formation of an intermediate imino bicyclic system (11a−c) which could be diastereoselectively reduced to substituted diamino alcohols 13a−c. The addition of an excess of PhLi to 1 in the presence of LiBr furnished disubstituted amine 19, the precursor of diphenyl[(2S)-piperidin-2-yl]methanamine (22).
compoundmethylpiperidinseriesdisubstituted amine 1939. SynthesisLiAlH 4 reductionOxazolopiperidinediphenylCyanodiamino alcohols 13cyano grouppiperidineAminoalkylpresencestrategysynthesisAsymmetric Synthesisaminoalkylhydrogenolysipiperidinformationdiamine 3LiBrPhLiimino bicyclic systemlithium derivativesprecursordiastereoselectively