Process for the preparation of aromatic derivatives of...

C - Chemistry – Metallurgy – 07 – C

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C07C 43/225 (2006.01) C07C 41/30 (2006.01) C07C 51/15 (2006.01) C07C 65/26 (2006.01)

Patent

CA 2631697

Process for the obtaining of 1 -adamantane (tricycle[3.3.1.1 (3,7)]decane) derivatives, or of a pharmaceutically acceptable salt thereof, based on a carboxylation reaction, via metallation, of a precursor compound with an adequate leaving group. It also comprises the preparation of the precursor compound by means of a selective coupling of the corresponding boron, magnesium or zinc derivative with the corresponding disubstitute aromatic derivative. It is especially useful for the obtaining of Adapalene at industrial scale with good yield and high purity.

L'invention concerne un procédé permettant d'obtenir des dérivés de 1 -adamantane (tricyclo[3.3.1.1 (3,7)]décane) ou un sel de qualité pharmaceutique de ceux-ci et basé sur une réaction de carboxylation, par métallation, d'un composé précurseur présentant un groupe partant adéquat. Le procédé consiste également à préparer le composé précurseur au moyen d'un couplage sélectif du dérivé de bore, magnésium ou zinc correspondant avec le dérivé aromatique disubstitué correspondant. Le procédé selon l'invention est spécialement utile pour obtenir l'adapalène à une échelle industrielle, avec un rendement élevé et une pureté élevée.

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