Transition-metal catalyzed synthesis of Ketoprofen

• Autor(a) principal: Ramminger,Carolina
• Data de Publicação: 2000
• Outros Autores: Zim,Danilo, Lando,Vanusa R., Fassina,Viviane, Monteiro,Adriano L.
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Journal of the Brazilian Chemical Society (Online)
• Texto Completo: http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0103-50532000000200002
• topic: ketoprofen; carbonylation; hydrovinylation; hydrogenation

Transition metal-catalyzed reactions including carbonylations, hydrovinylations and hydrogenations have been applied in the synthesis of alpha-(3-benzoylphenyl)propanoic acid (Ketoprofen). 3-Vinylbenzophenone was obtained from 3-bromobenzophenone by a Pd-catalyzed Heck coupling reaction. Pd-catalyzed carbonylation of this olefin gave the isopropyl alpha-(3-benzoylphenyl) propionate in high yield (95%) and with high regioselectivity (>99.5%). Ketoprofen was obtained in 90% yield by hydrolysis of the isopropyl ester. It was also obtained in two steps from 3-vinylbenzophenone by a Ni-catalyzed hydrovinylation selectively affording 3-(3'-benzoylphenyl)-1-butene, followed by an oxidation. 3-Ethynylbenzophenone was obtained from 3-bromobenzophenone by Pd-catalyzed coupling reaction. By means of a Pd-catalyzed carbonylation, this alkyne was converted regioselectively (97%) into methyl alpha-(3-benzoylphenyl) acrylate (93% yield). Hydrolysis of the ester afforded the alpha-(3-benzoylphenyl)acrylic acid. Asymmetric hydrogenation of this acid to give (S)-ketoprofen in 95% optical yield was achieved using a chiral Ru-(S)-BINAP catalyst.