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

doi:10.1007/s40242-014-3257-1

Abstract

Abstract:

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.

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]. Chemical Research in Chinese Universities, 2014, 30(2): 250-256.

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