New Synthesis of Diarylmethanes, Key Building Blocks for SGLT2 Inhibitors
Masahiko Seki, Sandeep Ramesharao Tapkir, Maheshwara Reddy Nadiveedhi, Shaheen Kasim Mulani, Kazushi Mashima
Abstract
High Resolution Image Download MS PowerPoint Slide Synthesis of diarylmethanes, a key building block for SGLT2 inhibitors, has been developed through ketone synthesis by Friedel–Crafts acylation with TiCl 4, followed by reduction with TiCl 4 /NaBH 4 . The new protocol proceeded more cleanly than the previous methods employing AlCl 3 and BF 3 ·OEt 2 /Et 3 SiH to provide the diarylmethanes corresponding to canagliflozin, empagliflozin, and luseogliflozin in a highly expedient and affordable manner. In the case of a diarylmethane for the synthesis of dapagliflozin, the reduction step took place by an alternative method using InCl 3 /Al/BF 3 ·OEt 2 .