Efficient synthesis of NK1 receptor antagonist aprepitant using a crystallization-induced diastereoselective transformation

…, TD Nelson, A Candelario, MA Huffman…

Index: Brands, Karel M. J.; Payack, Joseph F.; Rosen, Jonathan D.; Nelson, Todd D.; Candelario, Alexander; Huffman, Mark A.; Zhao, Matthew M.; Li, Jing; Craig, Bridgette; Song, Zhiguo J.; Tschaen, David M.; Hansen, Karl; Devine, Paul N.; Pye, Philip J.; Rossen, Kai; Dormer, Peter G.; Reamer, Robert A.; Welch, Christopher J.; Mathre, David J.; Tsou, Nancy N.; McNamara, James M.; Reider, Paul J. Journal of the American Chemical Society, 2003 , vol. 125, # 8 p. 2129 - 2135

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Citation Number: 119

Abstract

An efficient stereoselective synthesis of the orally active NK1 receptor antagonist Aprepitant is described. A direct condensation of N-benzyl ethanolamine with glyoxylic acid yielded a 2- hydroxy-1, 4-oxazin-3-one which was activated as the corresponding trifluoroacetate. A Lewis acid mediated coupling with enantiopure (R)-1-(3, 5-bis (trifluoromethyl) phenyl) ethan-1-ol afforded a 1: 1 mixture of acetal diastereomers which was converted into a ...