Facile Synthesis of Enantiomerically Pure1-(5-Bromo-2-chlorophenyl)-1-(4-ethoxyphenyl)ethane

doi:10.1007/s40242-014-3257-1

高等学校化学研究 ›› 2014, Vol. 30 ›› Issue (2): 250-256.doi: 10.1007/s40242-014-3257-1

Facile Synthesis of Enantiomerically Pure1-(5-Bromo-2-chlorophenyl)-1-(4-ethoxyphenyl)ethane

ZHANG Shuo^1,2, WANG Wenjin², LI Chuan², LIU Peng², XU Weiren², TANG Lida², WANG Jianwu¹, ZHAO Guilong²

1. School of Chemistry and Chemical Engineering, Shandong University, Jinan 250100, P. R. China;
2. Tianjin Key Laboratory of Molecular Design and Drug Discovery, Tianjin Institute of Pharmaceutical Research, Tianjin 300193, P. R. China

收稿日期:2013-06-13 修回日期:2013-07-15 出版日期:2014-04-01 发布日期:2013-08-30
通讯作者: WANG Jianwu, ZHAO Guilong E-mail:zhao_guilong@126.com;jwwang@sdu.edu.cn
基金资助:
Supported by the National Natural Science Foundation of China(No.21302141) and the Key Projects of Tianjin Science and Technology Support Plan, China(No.10ZCKFSH01300).

Facile Synthesis of Enantiomerically Pure1-(5-Bromo-2-chlorophenyl)-1-(4-ethoxyphenyl)ethane

ZHANG Shuo^1,2, WANG Wenjin², LI Chuan², LIU Peng², XU Weiren², TANG Lida², WANG Jianwu¹, ZHAO Guilong²

1. School of Chemistry and Chemical Engineering, Shandong University, Jinan 250100, P. R. China;
2. Tianjin Key Laboratory of Molecular Design and Drug Discovery, Tianjin Institute of Pharmaceutical Research, Tianjin 300193, P. R. China

Received:2013-06-13 Revised:2013-07-15 Online:2014-04-01 Published:2013-08-30
Contact: WANG Jianwu, ZHAO Guilong E-mail:zhao_guilong@126.com;jwwang@sdu.edu.cn
Supported by:
Supported by the National Natural Science Foundation of China(No.21302141) and the Key Projects of Tianjin Science and Technology Support Plan, China(No.10ZCKFSH01300).

摘要/Abstract

摘要：

A facile 7-step procedure for the synthesis of enantiomerically pure 1-(5-bromo-2-chlorophenyl)-1-(4-ethoxyphenyl)ethanes[(R)-2 and(S)-2] that started from (5-bromo-2-chlorophenyl)(4-ethoxyphenyl)methanone 3 was developed. The key step was the resolution of 2-(5-bromo-2-chlorophenyl)-2-(4-ethoxyphenyl)acetic acid 6 by crystallizations of its L-and D-menthyl esters 7 and 8 from petroleum ether to give optically pure enantiomers 9 and 10, respectively. The absolute configurations of the products were unambiguously determined by single-crystal X-ray diffractions of four key intermediates, 9, 10, 13 and 14. This procedure is characterized by inexpensiveness, scalabi-lity and ability to produce two individual enantiomers of a diarylethane with unambiguously determined absolute configurations and high enantiomeric purities.

关键词: Diarylethane, Diastereomer, Enantiomer, Resolution, SGLT2 inhibitor

Abstract:

Key words: Diarylethane, Diastereomer, Enantiomer, Resolution, SGLT2 inhibitor

ZHANG Shuo, WANG Wenjin, LI Chuan, LIU Peng, XU Weiren, TANG Lida, WANG Jianwu, ZHAO Guilong. Facile Synthesis of Enantiomerically Pure1-(5-Bromo-2-chlorophenyl)-1-(4-ethoxyphenyl)ethane[J]. 高等学校化学研究, 2014, 30(2): 250-256.

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Facile Synthesis of Enantiomerically Pure1-(5-Bromo-2-chlorophenyl)-1-(4-ethoxyphenyl)ethane

Facile Synthesis of Enantiomerically Pure1-(5-Bromo-2-chlorophenyl)-1-(4-ethoxyphenyl)ethane

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