The invention relates to a preparation method for dimemorfan
phosphate and preparation methods of dimemorfan
phosphate intermediates, and belongs to the field of pharmaceutical chemicals. The invention provides the synthesis method of the dimemorfan
phosphate intermediate 2-(4-methylphenyl)-N-[(cyclohexen-1-yl)ethyl]
acetamide. The 2-(4-methylphenyl)-N-[(cyclohexen-1-yl)ethyl]
acetamide is preparedby reacting 2-(1-cyclohexenyl)
ethylamine with p-methylphenylacetic acid. The invention also provides the synthesis method of the other dimemorfan phosphate intermediate 1-(4-methylbenzyl)-1,2,3,4,5,6,7,8-octahydroisoquinoline. The 1-(4-methylbenzyl)-1,2,3,4,5,6,7,8-octahydroisoquinoline is prepared by reducing 1-(4-methylbenzyl)-3,4,5,6,7,8-hexahydroisoquinoline. The invention also provides the preparation method for preparing dimemorfan phosphate from (9alpha,13alpha,14alpha)-3-methylmorphinan-17-carboxaldehyde. The invention further provides a
total synthesis method for preparing dimemorfanphosphate from the intermediates. The methods have the advantages of mild
reaction conditions, no dangerous reagents, obtaining of high-purity dimemorfan phosphate through a common salt forming reaction and recrystallization, simplicity in post-treatment, and suitableness for industrial large-scale production.