709031-41-4Relevant academic research and scientific papers
The effect of additives on the zinc carbenoid-mediated cyclopropanation of a dihydropyrrole
Ramirez, Antonio,Truc, Vu Chi,Lawler, Michael,Ye, Yun K.,Wang, Jianji,Wang, Chenchi,Chen, Steven,Laporte, Thomas,Liu, Nian,Kolotuchin, Sergei,Jones, Scott,Bordawekar, Shailendra,Tummala, Srinivas,Waltermire, Robert E.,Kronenthal, David
, p. 6233 - 6243 (2014)
The synthesis of a key intermediate in the preparation of oral antidiabetic drug Saxagliptin is discussed with an emphasis on the challenges posed by the cyclopropanation of a dihydropyrrole. Kinetic studies on the cyclopropanation show an induction period that is consistent with a change in the structure of the carbenoid reagent during the course of the reaction. This mechanistic transition is associated with an underlying Schlenk equilibrium that favors the formation of monoalkylzinc carbenoid IZnCH2I relative to dialkylzinc carbenoid Zn(CH2I)2, which is responsible for the initiation of the cyclopropanation. The factors influencing reaction rates and diastereoselectivities are discussed with the aid of DFT computational studies. The rate accelerations observed in the presence of Br?nsted acid-type additives correlate with the minimization of the undesired induction period and offer insights for the development of a robust process.
METHODS AND COMPOUNDS PRODUCING DIPEPTIDYL PEPTIDASE IV INHIBITORS AND INTERMEDIATES THEREOF
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Page 75, (2008/06/13)
Methods and compounds for production of cyclopropyl-fused pyrrolidine-based inhibitors of dipeptidyl peptidase IV are provided
