Process for the preparation of entacapone and intermediates...

C - Chemistry – Metallurgy – 07 – C

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C07C 255/51 (2006.01) C07C 253/30 (2006.01)

Patent

CA 2681027

New preparation process for the preparation of entacapone which comprises converting the 3,4-dimethoxy-5-nitrobenzoic acid into an activated derivative which is reacted with 2-cyano-N,N-diethylacetamide in the presence of a base to give 2-cyano-3-(3,4-dimethoxy-5-nitrophenyl)-N,N-diethyl-3- hydroxyacrylamide; reacting the resulting compound with MHB(OCOR)3 where R is (C1-C4)-alkyl, phenyl, or CF3; and M is a sodium, potassium or ((C1-C4)-alkyl)4N, in the presence of an appropriate solvent to give E-2-cyano- 3-3,4-dimethoxy-5-nitrophenyl)-N,N-diethylacrylamide; and finally submitting the compound obtained to a demethylation reaction to yield entacapone. Both 2-cyano-3-(3,4-dimethoxy-5-nitrophenyl)-N,N-diethyl-3-hydroxyacrylamide and E-2-cyano-3-3,4-dimethoxy-5-nitrophenyl)-N,N-diethylacrylamide are new. Entacapone has industrial applicability as antiparkinson's agent.

La présente invention porte sur un nouveau procédé de préparation d'entacapone. Ce procédé comprend les opérations consistant à convertir l'acide 3,4-diméthoxy-5-nitrobenzoïque en un dérivé activé qui est mis à réagir avec le 2-cyano-N,N-diéthylacétamide en présence d'une base pour donner le 2-cyano-3-(3,4-diméthoxy-5-nitrophényl)-N,N-diéthyl-3-hydroxyacrylamide ; faire réagir le composé résultant avec MHB(OCOR)3 où R représente alkyle en C1-C4, phényle ou CF3 ; et M représente sodium, potassium ou (alkyl en C1-C4 4N, en présence d'un solvant approprié, pour donner le E-2-cyano-3-3,4-diméthoxy-5-nitrophényl)-N,N-diéthylacrylamide ; et finalement soumettre le composé obtenu à une réaction de déméthylation pour fournir l'entacapone. Le 2-cyano-3-(3,4-diméthoxy-5-nitrophényl)-N,N-diéthyl-3-hydroxyacrylamide et le E-2-cyano-3-3,4-diméthoxy-5-nitrophényl)-N,N-diéthylacrylamide sont tous deux nouveaux. Une application industrielle de l'entacapone est l'application comme agent antiparkinsonien.

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