A scalable synthesis of the (S)-4-(tert-butyl)-2-(pyridin-2-yl)-4,5-dihydrooxazole ((S)-t-BuPyOx) ligand.
An efficient method for the synthesis of the (S)-4-(tert-butyl)-2-(pyridin-2-yl)-4,5-dihydrooxazole ((S)-t-BuPyOx) ligand has been developed. Inconsistent yields and tedious purification in known routes to (S)-t-BuPyOx suggested the need for an efficient, dependable, and scalable synthetic route. Furthermore, a route suitable for the synthesis of PyOx derivatives is desirable. Herein, we describe the development of a three-step route from inexpensive and commercially available picolinic acid. This short procedure is amenable to multi-gram scale synthesis and provides the target ligand in 64% overall yield.
The Warren and Katharine Schlinger Laboratory for Chemistry and Chemical Engineering, Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California 91125, USA ; Shionogi & Co., Ltd. 1-3, Kuise Terajima 2-chome Amagasaki, Hyogo 660-0813, Japan.
Hideki
H
Shimizu
Jeffrey C
JC
Holder
Brian M
BM
Stoltz
asymmetric catalysis; diamine ligands; optimization; synthesis