Syntheses of morpholine-2,3-diones and 2-hydroxymorpholin-3-ones: Intermediates in the synthesis of aprepitant

Tetrahedron Letters

Volumn 45, Issue 48, 2004, Pages 8917-8920

  Nelson, Todd D ^a   Rosen, Jonathan D ^a   Brands, Karel M J ^a   Craig, Bridgette ^a   Huffman, Mark A ^a   McNamara, James M ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

Amino alcohols; Lactam; Lactol; Morpholine 2,3 diones; Morpholine 3 ones

Indexed keywords

ALCOHOL DERIVATIVE; APREPITANT; BETA AMINO ACID; KETONE DERIVATIVE; MORPHOLINE DERIVATIVE;

ARTICLE; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; NUCLEAR MAGNETIC RESONANCE; POLYMERIZATION; SUBSTITUTION REACTION; SYNTHESIS; THERMODYNAMICS;

EID: 7544245974     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.tetlet.2004.09.185     Document Type: Article

References (15)

1. For a recent review of aprepitant, see: T.M. Dando, and C.M. Perry Drugs 64 2004 777
2. J.J. Hale, S.G. Mills, M. MacCoss, P.E. Finke, M.A. Cascieri, S. Sadowski, E. Ber, G.G. Chicchi, M. Kurtz, J. Metzger, G. Eiermann, N.N. Tsou, F.D. Tattersall, N.J.M. Rupniak, A.R. Williams, W. Rycroft, R. Hargreaves, and D.E. MacIntyre J. Med. Chem. 41 1998 4607
3. K.M.J. Brands, J.F. Payack, J.D. Rosen, T.D. Nelson, A. Candelario, M.A. Huffman, M.M. Zhao, J. Li, B. Craig, Z.J. Song, D.M. Tschaen, K. Hansen, P.N. Devine, P.J. Pye, K. Rossen, P.G. Dormer, R.A. Reamer, C.J. Welch, D.J. Mathre, N.N. Tsou, J.M. McNamara, and P.J. Reider J. Am. Chem. Soc. 125 2003 2129
4. K.B. Hansen, J.R. Chilenski, R. Desmond, P.N. Devine, E.J.J. Grabowski, R. Heid, M. Kubryk, D.J. Mathre, and R. Varsolona Tetrahedron: Asymmetry 14 2003 3581
5. For a recent review on the biological relevance and synthesis of C-substituted morpholine derivatives, see: R. Wijtmans, M.K.S. Vink, H.E. Schoemaker, F.L. van Delft, R.H. Blaauw, and F.P.J.T. Rutjes Synthesis 22 2004 641
6. For examples of the synthesis of morpholine-2,3-diones, see: W. Tam J. Org. Chem. 51 1986 2977
7. S.-I. Murashashi, Y. Mitsue, and K. Ike J. Chem. Soc., Chem. Commun. 1987 125
8. Y. Imada, Y. Mitsue, K. Ike, K.-i. Washizuka, and S.-I. Murashashi Bull. Chem. Soc. Jpn. 69 1996 2079
9. In a complimentary fashion, α-methylbenzylethanolamine has been prepared by the addition of α-methylbenzylamine to diethyloxalate followed by an LAH-mediated reduction of the resulting amide ester: D.C. Horwell, R.A. Lewthwaite, M.C. Pritchard, G.S. Ratcliffe, and J.R. Rubin Tetrahedron 54 1998 4591
10. M.M. Zhou, J.M. McNamara, G.-J. Ho, K.M. Emerson, Z.J. Song, D.M. Tschaen, K.M.J. Brands, U.H. Dolling, E.J.J. Grabowski, P.J. Reider, X. Cottrell, M.S. Ashwood, and B.C. Bishop J. Org. Chem. 67 2002 6743
11. D. Sicker, and H. Hartenstein Synthesis 1993 771
12. F. Chastrette, C. Bracoud, M. Chastrette, G. Mattioda, and Y. Christidis Bull. Soc. Chim. Fr. II 1985 66
13. A.M. Aman, and R.S. Brown J. Am. Chem. Soc. 121 1999 4598
14. H. Morawetz, and P.S. Otaki J. Am. Chem. Soc. 85 1963 463
15. 2O, then impurities are not completely rejected