An Efficient Large-Scale Synthesis of Methyl 5-[2-(2,5-Dimethoxyphenyl)ethyl]-2-hydroxybenzoate

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• 作者：Andrew Kucerovy ; Tangqing Li ; Kapa Prasad ; Oljan Repi<img src="http ; //pubs.acs.org/images/entities/ccaron.gif" border="0"> ; and Thomas J. Blacklock
• 刊名：Organic Process Research & Development
• 出版年：1997
• 出版时间：July 1997
• 年：1997
• 卷：1
• 期：4
• 页码：287 - 293
• 全文大小：162K
• 年卷期：v.1,no.4(July 1997)
• ISSN：1520-586X

文摘

Methyl 5-[2-(2,5-dimethoxyphenyl)ethyl]-2-hydroxybenzoate(1)is a new chemical entity designed by NovartisPharmaceuticalsCorporation for the treatment of hyperproliferative andinflammatory disorders and cancer. Development of aprototypeadequate process for its preparation is described. Thefinalizedprocess was six steps in length and started with the commercially available compounds 2,5-dimethoxybenzaldehhydeand 5-formylsalicylic acid. The methyl ester of5-formylsalicylicacid was condensed with dimethyl[(2,5-dimethoxyphenyl)methyl]phosphonate, prepared from2,5-dimethoxybenzaldehyde in three steps, to afford methyl5-[2-(2,5-dimethoxyphenyl)ethenyl]-2-hydroxy-(E)-benzoate. Without purification,thisintermediate was hydrogenated using 10% Pd/C at 40 <IMG SRC="/images/entities/deg.gif">Ctoafford 1, in >99.5% purity after recrystallization fromabsoluteethanol. The process research into theHorner-Wadsworth-Emmons-type olefination and a bromination reaction are alsodiscussed; improvements in these transformations permittedelimination of column chromatography.