An Efficient Large-Scale Process for the Human Leukocyte Elastase Inhibitor, DMP 777
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- 作者：Louis Storace ; Luigi Anzalone ; Pat N. Confalone ; Wayne P. Davis ; Joseph M. Fortunak ; Mark Giangiordano ; James J. Haley ; Jr. ; Kenneth Kamholz ; Hui-Yin Li ; Philip Ma ; William A. Nugent ; Rodney L. Parson
- 刊名：Organic Process Research & Development
- 出版年：2002
- 出版时间：January 2002
- 年：2002
- 卷：6
- 期：1
- 页码：54 - 63
- 全文大小：118K
- 年卷期：v.6,no.1(January 2002)
- ISSN：1520-586X
文摘
This report describes a new convergent, selective, and economical synthesis of DMP 777,1 ending with the coupling of the chiral
-lactam half of the molecule (1) to the chiral amine as theisocyanate (2). Other steps involve the coupling of the -lactam3 to the phenolic moiety under phase-transfer conditions,followed by resolution of the resulting piperazine derivativeusing a chiral acid, and recycling of the undesired enantiomeralso under phase-transfer conditions. The chiral amine 4 wasproduced efficiently starting from (R)-
-methylbenzylamine andthe corresponding butyrophenone.
-lactam half of the molecule (1) to the chiral amine as theisocyanate (2). Other steps involve the coupling of the -lactam3 to the phenolic moiety under phase-transfer conditions,followed by resolution of the resulting piperazine derivativeusing a chiral acid, and recycling of the undesired enantiomeralso under phase-transfer conditions. The chiral amine 4 wasproduced efficiently starting from (R)--methylbenzylamine andthe corresponding butyrophenone.