Green chemistry approach to the synthesis of N-substituted piperidones.
An efficient green chemistry approach to the synthesis of N-substituted piperidones and piperidines was developed and applied to the synthesis of 1-(2-pyridinylmethyl)-piperidin-4-one, 1, a key starting material for the synthesis of LY317615, an antiangiogenic agent currently under development at Eli Lilly and Company (Chart 1).(1) The general utility of this methodology, which presents significant advantages over the classical Dieckman approach to this class of compounds, was also demonstrated by the direct synthesis of a series of substituted piperidones and piperidines, including potential dopamine D4 receptor antagonists 2 and 3, that have been evaluated in the clinic as antipsychotic agents (Chart 2).(2)
Faul
Margaret M
MM
Lilly Research Laboratories, A Division of Eli Lilly and Company, Chemical Process Research and Development Division, Eli Lilly and Co., Indianapolis, Indiana 46285-4813, USA.
Kobierski
Michael E
ME
Kopach
Michael E
ME
D004787:Environmental Pollution / Q000517:prevention & control; D006576:Heterocyclic Compounds, 4 or More Rings / Q000138:chemical synthesis; D010880:Piperidines / Q000138:chemical synthesis; D010881:Piperidones / Q000138:chemical synthesis*
D006576:Heterocyclic Compounds, 4 or More Rings; D010880:Piperidines; D010881:Piperidones