药物Empagliflozin(艾格列净、恩格列净)合成检索总结报告

参考文献
US2011/237789; (2011); (A1) English; US2011/237526; (2011); (A1) English.
2
(containing residual n-heptane, which explains the yield
Hale Waihona Puke of >100%). The identity of the product is determined via
infrared spectrometry.
To a solution of N-methylmorpholine (246.8 mL, 2.24 mol)
and (3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)-
tetrahydropyran-2-one 1 (50 g, 0.28 mol, purchased from
Aladdin) in anhydroustetrahydrofuran (500 mL) was added
dropwise trimethylchlorosilane (213 mL, 1.68 mol) over
操作方法 aperiod of 2hours. The mixture was stirred at room
合成方法
操作方法 一
实验步骤
A suspension of the D-(+)-gluconic acid-delta-lactone 1 (42.0 kg), tetrahydrofuran (277.2 kg), 4-methylmorpholine (NMM; 152.4 kg) and 4-dimethylaminopyridine (DMAP; 1.44 kg) is treated with chlorotrimethylsilane (TMSCl; 130.8 kg) within 50 min at 13 to 19°C. After completion of the addition stirring is continued for 1 hr 30 min at 20 to 22°C. and the conversion is determined via HPLC analysis. Then n-heptane (216.4 kg) is added and the mixture is cooled to 5°C. Water (143 kg) is added at 3 to 5°C. within 15 min. After completion of the addition the mixture is heated to 15°C. and stirred for 15 min. The stirrer is switched off and the mixture is left stand for 15 min. Then the phases are separated and the organic layer is washed in succession two times with water (143 kg each). Then solvent is distilled off at 38°C. under reduced pressure and n-heptane (130 kg) is added to the residue. The resulting solution is filtered and the filter is rinsed with n-heptane (63 kg) (filter solution and product solution are combined). Then solvent is distilled off at 39 to 40°C. under reduced pressure. The water content of the residue is determined via Karl-Fischer analysis (result: 0.0%). 112.4 kg of the product 2 is obtained as an oil
二
temperature for 8 hours and quenched with water (1L). The
WO2015/43473; (2015); (A1) English
organiclayer waswashed with saturated aqueous dipotassium
hydrogen phosphate trihydrate (100 ml×3) and
英文名称：Empagliflozin 中文名称：艾格列净、恩格列净
本文主要对 Empagliflozin（艾格列净、恩格列净）的合成路线、 关键中间体的合成方法及实验操作方法进行了文献检索并作出了总 结。
二、Empagliflozin（艾格列净、恩格列净）合成路线
1
三、Empagliflozin（艾格列净、恩格列净）合成检索总结报告 (一) Empagliflozin（艾格列净、恩格列净）中间体 2 的合成
saturatedaqueous sodium chloride (100 mL×3), dried over
anhydrous sodium sulfate and concentrated in vacuo. The
Empagliflozin（艾格列净、恩格列净）合成检索总结报告
一、Empagliflozin（艾格列净、恩格列净）简介 Empagliflozin（艾格列净、恩格列净）于 2014 年 8 月 1 日在美 国上市。Empagliflozin（艾格列净、恩格列净）是 SGLT2 抑制剂，适 应于 2 型糖尿病。Empagliflozin（艾格列净、恩格列净）不良反应有： 尿路感染和女性霉菌性外阴感染。 Empagliflozin（艾格列净、恩格列净）分子结构式如下: