Synthesis of a Precursor to Sacubitril Using Enabling Technologies
Bourne, Samuel L
Machine‐Assisted Synthesis of a Precursor to Sacubitril
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Lau, S. H., Bourne, S. L., Martin, B., Schenkel, B., Penn, G., & Ley, S. (2015). Synthesis of a Precursor to Sacubitril Using Enabling Technologies. Organic Letters, 17 5436-5439. https://doi.org/10.1021/acs.orglett.5b02806
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-catalysed 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.
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).
External DOI: https://doi.org/10.1021/acs.orglett.5b02806
This record's URL: https://www.repository.cam.ac.uk/handle/1810/251238
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