The invention discloses a preparation method of dimethylmorphinan
phosphate used as a
cough medicine. The method comprises the following steps: removing L-
mandelic acid from (S)-l-(4-methylbenzyl)-1,2,3,4,5,6,7,8-octahydroisoquinoline-L-mandelate to obtain (S)-l-(4-methylbenzyl)-1,2,3,4,5,6,7,8-octahydroisoquinoline, performing
methylation by using the (S)-l-(4-methylbenzyl)-1,2,3,4,5,6,7,8-octahydroisoquinoline chiral material as a
raw material, and then performing cyclization reaction together with
phosphoric acid under the conditions of heating and decompression to obtain (9S,13S,14S)-3,17-dimethylmorphinan monophosphate with three chiral centers, namely dimethylmorphinan
phosphate; and desalting, rectifying, crystallizing, salifying,
drying, and packaging to obtain the refined dimethylmorphinan
phosphate product. The method has the characteristics of simple process, low cost, high yield, high product purity, short
production cycle and the like, thereby being a synthetic
route suitable for industrial
mass production.