An Efficient Large-Scale Process for the Human Leukocyte Elastase Inhibitor, DMP 7771

This report describes a new convergent, selective, and economical synthesis of DMP 777, ending with the coupling of the chiral β-lactam half of the molecule (1) to the chiral amine as the isocyanate (2). Other steps involve the coupling of the β-lactam 3 to the phenolic moiety under phase-transfer c...

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Bibliographic Details
Published in:Organic process research & development 2002-01, Vol.6 (1), p.54-63
Main Authors: Storace, Louis, Anzalone, Luigi, Confalone, Pat N, Davis, Wayne P, Fortunak, Joseph M, Giangiordano, Mark, Haley, James J, Kamholz, Kenneth, Li, Hui-Yin, Ma, Philip, Nugent, William A, Parsons, Rodney L, Sheeran, Patrick J, Silverman, Charlotte E, Waltermire, Robert E, Wood, Christopher C
Format: Article
Language:English
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Summary:This report describes a new convergent, selective, and economical synthesis of DMP 777, ending with the coupling of the chiral β-lactam half of the molecule (1) to the chiral amine as the isocyanate (2). Other steps involve the coupling of the β-lactam 3 to the phenolic moiety under phase-transfer conditions, followed by resolution of the resulting piperazine derivative using a chiral acid, and recycling of the undesired enantiomer also under phase-transfer conditions. The chiral amine 4 was produced efficiently starting from (R)-α-methylbenzylamine and the corresponding butyrophenone.
ISSN:1083-6160
1520-586X
DOI:10.1021/op015507o