An Improved Synthesis of
(4-{4-Hydroxy-3-isopropyl-5-[(4-nitrophenyl)ethynyl]benzyl}-3,5-dimethylphenoxy)acetic
Acid (NH-3)

Madathil B. Gopinathan; Kenneth S. Rehder

doi:10.1055/s-0028-1088041

SHORTPAPER

An Improved Synthesis of (4-{4-Hydroxy-3-isopropyl-5-[(4-nitrophenyl)ethynyl]benzyl}-3,5-dimethylphenoxy)acetic Acid (NH-3)

Madathil B. Gopinathan, Kenneth S. Rehder*
RTI International, Center for Organic and Medicinal Chemistry, Research Triangle Park, NC 27709-2194, USA
Fax: +1(919)5418868; e-Mail: krehder@rti.org;

Abstract

Alle Artikel dieser Rubrik

Abstract

Sonogashira coupling of methyl {4-[3-iodo-5-isopropyl-4-(methoxymethoxy)benzyl]-3,5-dimethylphenoxy}acetate with (trimethylsilyl)acetylene afforded the corresponding (trimethylsilyl)ethynyl derivative in quantitative yield. Copper-free palladium-catalyzed coupling of this intermediate with 1-iodo-4-nitrobenzene afforded methyl (4-{3-isopropyl-4-(methoxymethoxy)-5-[(4-nitrophenyl)ethynyl]benzyl}-3,5-dimethylphenoxy)acetate in high yield. Saponification of the ester group, followed by the removal of the methoxymethyl group afforded (4-{4-hydroxy-3-isopropyl-5-[(4-nitrophenyl)ethynyl]benzyl}-3,5-dimethylphenoxy)acetic acid (NH-3).

Key words

coupling - Sonogashira coupling - palladium catalysis - 1-iodo-4-nitrobenzene - hydrolysis

Volltext

Referenzen

References

<A NAME="RM06808SS-1">1</A> Lazar MA. Endocr. Rev. 1993, 14: 184

<A NAME="RM06808SS-2A">2a</A> Koehler K. Gordon S. Brandt P. Carlsson B. Backsbro-Saeidi A. Apelqvist T. Agback P. Grover GJ. Nelsson W. Grynfarb M. Farnegardh M. Rehnmark S. Malm J. J. Med. Chem. 2006, 49: 4635

<A NAME="RM06808SS-2B">2b</A> Malm J. Gordon S. Brandt P. Carlsson B. Agback P. Saeidi AB. Sandberg J. Bioorg. Med. Chem. Lett. 2007, 17: 2018

<A NAME="RM06808SS-3">3</A> Lim W. Nguyen NH. Yang HY. Scanlan TS. Furlow JD. J. Biol. Chem. 2002, 277: 35664

<A NAME="RM06808SS-4">4</A> Grover GJ. Dunn C. Nguyen NH. Boulet J. Dong G. Domogauer J. Barbounis P. Scanlan TS. J. Pharmacol. Exp. Ther. 2007, 322: 385

<A NAME="RM06808SS-5">5</A> Nguyen NH. Apriletti JW. Cunha Lima ST. Webb P. Baxter JD. Scanlan TS. J. Med. Chem. 2002, 45: 3310

<A NAME="RM06808SS-6">6</A> Nguyen NH. Apriletti JW. Baxter JD. Scanlan TS. J. Am. Chem. Soc. 2005, 127: 4599

<A NAME="RM06808SS-7">7</A> Takahashi S. Kuroyama Y. Sonogashira K. Hagihara N. Synthesis 1980, 627

The spectral properties of the impurity were suggestive of a substituted benzofuran, but this was not verified.