Process Development in the Synthesis of the ACE Intermediate MDL 28,726

Process Development in the Synthesis of the ACE Intermediate MDL 28,726

MDL 28,726 is a key intermediate in the synthesis of the ACE inhibitors MDL 27,210A and MDL 100,240. An efficient nine-step synthesis of this tricyclic acid, which has three chiral centers, was developed beginning with 3,4-dihydro-2H-pyran. A key step in the synthesis features an enzyme-catalyzed re...

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Veröffentlicht in:Organic process research & development 1999, Vol.3 (4), p.241-247
Hauptverfasser: Horgan, Stephen W, Burkhouse, David W, Cregge, Robert J, Freund, David W, LeTourneau, Michael, Margolin, Alexey, Webster, Mark E, Henton, Daniel R, Barton, Kathy P, Clouse, Robert C, DesJardin, Michael A, Donaldson, Richard E, Fetner, Neal J, Goralski, Christian T, Heinrich, Gerald P, Hoops, John F, Keaten, Robert T, McConnell, J. Russell, Nitz, Mark A, Stolz-Dunn, Sandra K
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container_end_page 247
container_issue 4
container_start_page 241
container_title Organic process research & development
container_volume 3
creator Horgan, Stephen W
Burkhouse, David W
Cregge, Robert J
Freund, David W
LeTourneau, Michael
Margolin, Alexey
Webster, Mark E
Henton, Daniel R
Barton, Kathy P
Clouse, Robert C
DesJardin, Michael A
Donaldson, Richard E
Fetner, Neal J
Goralski, Christian T
Heinrich, Gerald P
Hoops, John F
Keaten, Robert T
McConnell, J. Russell
Nitz, Mark A
Stolz-Dunn, Sandra K
description MDL 28,726 is a key intermediate in the synthesis of the ACE inhibitors MDL 27,210A and MDL 100,240. An efficient nine-step synthesis of this tricyclic acid, which has three chiral centers, was developed beginning with 3,4-dihydro-2H-pyran. A key step in the synthesis features an enzyme-catalyzed resolution of the lithium salt of the N-trifluoroacetamide of (R,S)-6-hydroxynorleucine. All of the steps were optimized and completed in reactor equipment using environmentally acceptable processes. Process development of this route is described.
doi_str_mv 10.1021/op970125x
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