Transition-metal catalyzed synthesis of Ketoprofen
| Autor: | Ramminger Carolina, Zim Danilo, Lando Vanusa R., Fassina Viviane, Monteiro Adriano L. |
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| Jazyk: | angličtina |
| Rok vydání: | 2000 |
| Předmět: | |
| Zdroj: | Journal of the Brazilian Chemical Society, Vol 11, Iss 2, Pp 105-111 (2000) |
| Druh dokumentu: | article |
| ISSN: | 0103-5053 35059966 |
| Popis: | 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. |
| Databáze: | Directory of Open Access Journals |
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