Bridgette Craig

Publications (3)18.45 Total impact

• Article: Synthesis of a potent hNK-1 receptor antagonist via an SN2 reaction of an enantiomerically pure alpha-alkoxy sulfonate.

  Todd D Nelson, Jonathan D Rosen, Jacqueline H Smitrovich, Joseph Payack, Bridgette Craig, Louis Matty, Mark A Huffman, James McNamara
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  ABSTRACT: The concise synthesis of a stereochemically rich hNK-1 receptor antagonist is described. The synthesis is highlighted by an S(N)2 reaction of an enantiomerically pure alpha-alkoxy sulfonate (orthogonally protected butane triol), which was prepared by utilizing salen-mediated hydrolytic kinetic resolution technology. A stereocontrolled acetalization was employed to connect two enantiomerically pure fragments with a high degree of diastereoselectivity.
  Organic Letters 02/2005; 7(1):55-8. · 5.86 Impact Factor
• Article: Efficient synthesis of NK(1) receptor antagonist aprepitant using a crystallization-induced diastereoselective transformation.

  Karel M J Brands, Joseph F Payack, Jonathan D Rosen, Todd D Nelson, Alexander Candelario, Mark A Huffman, Matthew M Zhao, Jing Li, Bridgette Craig, Zhiguo J Song, [......], Paul N Devine, Philip J Pye, Kai Rossen, Peter G Dormer, Robert A Reamer, Christopher J Welch, David J Mathre, Nancy N Tsou, James M McNamara, Paul J Reider
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  ABSTRACT: An efficient stereoselective synthesis of the orally active NK(1) 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 single isomer via a novel crystallization-induced asymmetric transformation. The resulting 1,4-oxazin-3-one was converted via a unique and highly stereoselective one-pot process to the desired alpha-(fluorophenyl)morpholine derivative. Interesting and unexpected [1,2]-Wittig and [1,3]-sigmatropic rearrangements were identified during the optimization of these key steps. In the final step, a triazolinone side chain was appended to the morpholine core. The targeted clinical candidate was thus obtained in 55% overall yield over the longest linear sequence.
  Journal of the American Chemical Society 03/2003; 125(8):2129-35. · 9.91 Impact Factor
• Article: Syntheses of morpholine-2,3-diones and 2-hydroxymorpholin-3-ones: intermediates in the synthesis of aprepitant

  Todd D. Nelson, Jonathan D. Rosen, Karel M.J. Brands, Bridgette Craig, Mark A. Huffman, James M. McNamara
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  ABSTRACT: The preparation of morpholine-2,3-diones and 2-hydroxymorpholin-3-ones from N-substituted β-amino alcohols is reported. These were useful intermediates in the synthesis and development of aprepitant.Graphical abstract
  Tetrahedron Letters 45(48):8917-8920. · 2.68 Impact Factor