Synthesis of a Precursor to Sacubitril Using Enabling Technologies
An efficient preparation of a precursor to the neprilysin inhibitor sacubitril is described. The convergent synthesis features a diastereoselective Reformatsky-type carbethoxyallylation and a rhodium-catalyzed stereoselective hydrogenation for installation of the two key stereocenters. Moreover, by...
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| Veröffentlicht in: | Organic letters 2015-11, Vol.17 (21), p.5436-5439 |
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| container_end_page | 5439 |
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| container_issue | 21 |
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| container_title | Organic letters |
| container_volume | 17 |
| creator | Lau, Shing-Hing Bourne, Samuel L Martin, Benjamin Schenkel, Berthold Penn, Gerhard Ley, Steven V |
| description | An efficient preparation of a precursor to the neprilysin inhibitor sacubitril is described. The convergent synthesis features a diastereoselective Reformatsky-type carbethoxyallylation and a rhodium-catalyzed stereoselective hydrogenation for installation of the two key stereocenters. Moreover, by integrating machine-assisted methods with batch processes, this procedure allows a safe and rapid production of the key intermediates which are promptly transformed to the target molecule (3·HCl) over 7 steps in 54% overall yield. |
| doi_str_mv | 10.1021/acs.orglett.5b02806 |
| format | Article |
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| ispartof | Organic letters, 2015-11, Vol.17 (21), p.5436-5439 |
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| source | MEDLINE; ACS Publications |
| subjects | Aminobutyrates - chemical synthesis Aminobutyrates - chemistry Aminobutyrates - pharmacology Catalysis Drug Combinations Hydrogenation Molecular Structure Neprilysin - antagonists & inhibitors Rhodium - chemistry Stereoisomerism Tetrazoles - chemical synthesis Tetrazoles - chemistry Tetrazoles - pharmacology |
| title | Synthesis of a Precursor to Sacubitril Using Enabling Technologies |
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