Practical asymmetric synthesis of aprepitant, a potent human NK-1 receptor antagonist, via a stereoselective Lewis acid-catalyzed trans acetalization reaction

…, KMJ Brands, UH Dolling, EJJ Grabowski…

Index: Zhao, Matthew M.; McNamara, James M.; Ho, Guo-Jie; Emerson, Khateeta M.; Song, Zhiguo J.; Tschaen, David M.; Brands, Karel M. J.; Dolling, Ulf-H; Grabowski, Edward J. J.; Reider, Paul J.; Cottrell, Ian F.; Ashwood, Michael S.; Bishop, Brian C. Journal of Organic Chemistry, 2002 , vol. 67, # 19 p. 6743 - 6747

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Citation Number: 49

Abstract

A streamlined and high-yielding synthesis of aprepitant (1), a potent substance P (SP) receptor antagonist, is described. The enantiopure oxazinone 16 starting material was synthesized via a novel crystallization-induced dynamic resolution process. Conversion of 16 to the penultimate intermediate cis-sec-amine 9 features a highly stereoselective Lewis acid-catalyzed trans acetalization of chiral alcohol 3 with trichloroacetimidate 18 followed ...