title: Efficient synthesis of Empagliflozin, an inhibitor of SGLT-2, utilizing an AlCl3-promoted silane reduction of a β-glycopyranoside.
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.
authors: Chemical Development, Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, Connecticut 06877, United States.
authors: Xiao-jun
authors: XJ
authors: Wang
authors: Li
authors: L
authors: Zhang
authors: Denis
authors: D
authors: Byrne
authors: Larry
authors: L
authors: Nummy
authors: Dirk
authors: D
authors: Weber
authors: Dhileep
authors: D
authors: Krishnamurthy
authors: Nathan
authors: N
authors: Yee
authors: Chris H
authors: CH
authors: Senanayake
mesh_terms: D000077410:Aluminum Chloride; D017607:Aluminum Compounds / Q000737:chemistry*; D001559:Benzhydryl Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002712:Chlorides / Q000737:chemistry*; D005960:Glucosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D007004:Hypoglycemic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D010084:Oxidation-Reduction; D012821:Silanes / Q000737:chemistry*; D000077203:Sodium-Glucose Transporter 2 Inhibitors
chemical_list: D017607:Aluminum Compounds; D001559:Benzhydryl Compounds; D002712:Chlorides; D005960:Glucosides; D007004:Hypoglycemic Agents; D012821:Silanes; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D000077410:Aluminum Chloride; C570240:empagliflozin