Synthesis of a Precursor to Sacubitril Using Enabling Technologies.
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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.
Description
Journal Title
Org Lett
Conference Name
Journal ISSN
1523-7060
1523-7052
1523-7052
Volume Title
17
Publisher
American Chemical Society (ACS)
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Rights and licensing
Except where otherwised noted, this item's license is described as Creative Commons Attribution 4.0 International License
Sponsorship
Engineering and Physical Sciences Research Council (EP/K009494/1)
Engineering and Physical Sciences Research Council (EP/K039520/1)
Engineering and Physical Sciences Research Council (EP/K039520/1)
We are grateful to Croucher Foundation (S.-H. L.) Novartis Pharma AG (S. L. B.) and the EPSRC (S. V. L., Grant Nos. EP/K0099494/1 and EP/K039520/1) for financial support. The crystallographic results in this paper were provided by Dr Andrew D. Bond (University of Cambridge).