The regioselective bromine-lithium exchange reaction of alkoxymethyldibromobenzene: A new strategy for the synthesis of tofogliflozin as a SGLT2 inhibitor for the treatment of diabetes. Issue 6 (9th February 2017)

• Record Type: Journal Article
• Authors: Murakata, Masatoshi; Ikeda, Takuma; Kimura, Nobuaki; Kawase, Akira; Nagase, Masahiro; Kimura, Masahiro; Maeda, Kenji; Honma, Akie; Shimizu, Hitoshi
• Is Part Of: Tetrahedron. Volume 73:Issue 6(2017)
• Page Start: 655
• Page End: 660
• Publication Date: 2017-02-09
• Subjects: Bromine-lithium exchange reaction -- Regioselective -- Sequential metalation-functionalization -- Tofogliflozin; Chemistry, Organic -- Periodicals; 547.005
• DOI: 10.1016/j.tet.2016.12.028
• Languages: English
• ISSNs: 0040-4020

Abstract

Abstract: The regioselective bromine-lithium exchange reaction of 2, 4-dibromo-1-(1-methoxy-1-methylethoxymethyl)benzene (2 ), which resulted in optimized selectivity of 220:1, is described. Applying this method to the synthesis of tofogliflozin (1 ) as a SGLT2 inhibitor is also described. Selective and sequential metalation-functionalization of2 led to the synthesis of1 in 47% overall yield. Graphical abstract: Highlights: Highly regioselective bromine-lithium exchange reaction of dibromobenzene derivative was realized. Dibromide as a starting material was found to be a mediator that increased the selectivity. Tofogliflozin was synthesized via three-component coupling.