| 摘要 |
A process for the preparation of the compound N-cyclopropylmethyl-6,14-endoethano-7-(2-hydroxy-2-methyl-2-ter-butyl)-tetrahydronororipavine which comprises reacting thebaine with acrolein to undergo Diels-Alder reaction to give 6,14-endoethano-7-formyl-tetrahydrothe-baine. This is reacted with methyl magnesium iodide to give 6,14-endoethano-7-(2-hydroxy-2-methyl)-tetrahydrothebaine which is oxidized by reaction with potassium permanganate to give 6,14-endoethano-7-acetyl-tetrahydrothebaine which is hydrogenated using palladium catalyst to give 6,14-endoethano-7-acetyltetrahydrothebaine. Reaction with ter-butyl magnesium chloride gives 6,14-endoethano-7-(2-hydroxy-2-methyl-2-ter-butyl)-tetxahydrothebaine which is reacted with cyanogen bromide to give N-cyano-6,14-endoethano-7-(2-hydroxy-2-methyl-2-ter-butyl) tetrahydrothebaine which is reacted with cyanoyen bromide to give N-cyano-6,14-endoethano-7-(2-hydroxy-2-methyl-2-terbutyl)-tetrahydrothebaine which is demethylated by treatment with potassium hydroxide in one pot at 210.degree.C to give 6,14-endoethano-7-(2-hydroxy-2-methyl-2-ter-butyl)-tetra-hydronororipavine which on treatment with cyclo-propyl methyl bromide gives the compound N-cyclo-propylmethyl-6,14-endoethano-7-(2-hydroxy-2-methyl-2-ter-butyl)-tetra-hydronororipavine. The process proceeds smoothly with readily available reactants, and yields a pure product, advantages over the prior art. |
