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.
MeSH terms
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Aluminum Chloride
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Aluminum Compounds / chemistry*
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Benzhydryl Compounds / chemical synthesis*
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Benzhydryl Compounds / chemistry
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Benzhydryl Compounds / pharmacology*
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Chlorides / chemistry*
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Glucosides / chemical synthesis*
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Glucosides / chemistry
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Glucosides / pharmacology*
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Hypoglycemic Agents / chemical synthesis*
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Hypoglycemic Agents / chemistry
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Hypoglycemic Agents / pharmacology*
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Molecular Structure
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Oxidation-Reduction
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Silanes / chemistry*
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Sodium-Glucose Transporter 2 Inhibitors*
Substances
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Aluminum Compounds
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Benzhydryl Compounds
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Chlorides
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Glucosides
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Hypoglycemic Agents
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Silanes
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Sodium-Glucose Transporter 2 Inhibitors
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Aluminum Chloride
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empagliflozin