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Paper | Regular issue | Vol 92, No. 9, 2016, pp.1599-1613
Published online, 11th July, 2016
DOI: 10.3987/COM-16-13484
An Efficient and Practical Preparation of a Potent Low-Affinity Na+-Dependent Glucose Cotransporter (SGLT2) Inhibitor, Sergliflozin Etabonate

Masahiro Kobayashi,* Hidetoshi Isawa, Junichi Sonehara, and Minoru Kubota

*Quality Assurance, Kissei Pharmaceutical Co., Ltd, 19-48 Yoshino, Matsumoto-City, Nagano-Pref., Japan

Abstract

The development of an efficient and practical process for the preparation of Sergliflozin etabonate (1), a prodrug of a novel selective low-affinity Na+-dependent glucose cotransporter (SGLT2) inhibitor, Sergliflozin (2), is described. Its development required a suitable process for large-scale manufacturing. We established a chromatography-free approach for 2-[(4-methoxyphenyl)methyl]phenol (5), the efficient O-glycosylation of 5 with penta-O-acetyl-β-D-glucopyranose (7) without using a trichloroimidate intermediate (9), and efficient reaction conditions to introduce an ethoxycarbonyl group onto the primary alcohol of 2 with high selectivity. This process provided 1 with a 45% overall yield from anisole (10).