Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Aminobutyrates / chemical synthesis*
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Aminobutyrates / chemistry
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Aminobutyrates / pharmacology
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Biphenyl Compounds
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Catalysis
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Drug Combinations
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Hydrogenation
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Molecular Structure
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Neprilysin / antagonists & inhibitors*
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Rhodium / chemistry
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Stereoisomerism
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Tetrazoles / chemical synthesis*
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Tetrazoles / chemistry
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Tetrazoles / pharmacology
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Valsartan
Substances
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Aminobutyrates
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Biphenyl Compounds
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Drug Combinations
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Tetrazoles
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Valsartan
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Rhodium
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Neprilysin
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sacubitril and valsartan sodium hydrate drug combination