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A comparative study on the photo-induced arylation of β-dicarbonyl compounds by arylazosulfides and its use in the synthesis of methyl labeled 2-arylpropionic acids

✍ Scribed by Mercè Tona; Francisco Sánchez-Baeza; Angel Messeguer


Publisher
Elsevier Science
Year
1994
Tongue
French
Weight
858 KB
Volume
50
Category
Article
ISSN
0040-4020

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✦ Synopsis


A comparative study on the arylation of ~dicarbony1 derivatives (acetylacetone, methyl acetoacetate and dimethyl malonate) by using the photdnduced decomposition of arylazodfide.s is presented. The arylazadfides used oootained~~lmoietiesreletedtaKetopofenormuprofenandthcreactionwasperfamcdfollowingthe~~reported by D&E&a et al. (Tetrahedron, 1991.47.333). From the aryedes assayed. only those beating a c&my1 group ~tothebartenering,i.e.,landll.~~the~ alylationafldl&iinsatislactoryyields.ColNmlingtlle gdicarbonyrduivati~condensah 'onof~~intheclreeof1andofdimcthylmalaoateinthatof11~vethebest ltmlts. Howevex, the further methylation of the aryl ~dicdollyl %lduct wa9 cldy advantageolls for the case of the 2arylmalmate derivatives. The use of this syntktk strategy for the convenient prqmation of Ketoprofen (23% overall yield, 7 steps from Ini~) and Ibuprofen (34% overall yield, 8 steps from 4-iwbutyrylbemene) isotopomexs labeled at themethy1groupatc-2isalsoqorted. 2-Atylpropionic acids constitute an important group of non-steroidal anti inflammatory drugs and their therapeutic value has been demonstrated by the introduction and extensive use of several compounds in the