Efficient Synthesis of Empagliflozin, an Inhibitor of SGLT-2, Utilizing an AlCl3-Promoted Silane Reduction of a β-Glycopyranoside
Organic Letters2014Vol. 16(16), pp. 4090–4093
Citations Over TimeTop 10% of 2014 papers
Xiao‐jun Wang, Li Zhang, Denis Byrne, Larry J. Nummy, Dirk Weber, Dhileep Krishnamurthy, Nathan K. Yee, Chris H. Senanayake
Abstract
An efficient production synthesis of the SGLT-2 inhibitor Empagliflozin (5) from acid 1 is described. The key tactical stage involves I/Mg exchange of aryl iodide 2 followed by addition to glucono lactone 3 in THF. Subsequent in situ treatment of the resulting lactol with HCl in MeOH produces β-anomeric methyl glycopyranoside 4 which is, without isolation, directly reduced with Et3SiH mediated by AlCl3 as a Lewis acid in CH2Cl2/MeCN to afford 5 in 50% overall yield. The process was implemented for production on a metric ton scale for commercial launch.
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