Improved process for making apomorphine and apocodeine

C - Chemistry – Metallurgy – 07 – D

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C07D 221/18 (2006.01)

Patent

CA 2648045

There is provided an improved and convenient process for the synthesis of aporphines, such as apomorphine and apocodeine, by the rearrangement of the corresponding morphine or codeine derivatives. The use of a suitable water scavenger in an acid catalyzed rearrangement of the morphine derivatives unexpectedly results in a reaction temperature convenient for plant operation without sacrificing product. The method of the present invention also alleviates the cumbersome operations that were employed in the prior art to eliminate water from the reaction mixture at the elevated temperatures. This process is adaptable for the general preparation of other aporphines from the corresponding morphine congeners.

La présente invention concerne un procédé amélioré et pratique de synthèse d'aporphines telles que l'apomorphine et l'apocodéine par un réarrangement des dérivés de morphine ou de codéine correspondants. L'utilisation d'un capteur d'eau adapté dans un réarrangement catalysé par un acide des dérivés de morphine permet de façon surprenante l'obtention d'une température de réaction adaptée à un procédé industriel sans gaspiller du produit. La méthode selon la présente invention facilite également les opérations peu ergonomiques employées dans l'art antérieur pour éliminer l'eau du mélange réactionnel à température élevée. Ce procédé est adaptable à la préparation générale d'autres aporphines à partir des analogues correspondants de morphine.

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