The invention relates to a preparation method of enclomiphene. The preparation method comprises steps as follows: (1) clomiphene or salt thereof and racemic 1,1'-binaphthyl-2,2'-diyl hydrogenphosphate are subjected to a reaction in alcohol solvents containing ether solvents, and an enclomiphene and 1,1'-binaphthyl-2,2'-diyl hydrogenphosphate compound in a solid form is obtained; (2) the enclomiphene and 1,1'-binaphthyl-2,2'-diyl hydrogenphosphate compound in a solid form is subjected to a free reaction, and enclomiphene is prepared. With the alcohol solvents containing the ether solvents as splitting solvents, enclomiphene and the splitting solvents can form a solid compound which is directly separated out from the splitting solvents, the flowability of a reaction system is improved, and the enclomiphene preparation method with better industrial application prospects is provided, and by means of the preparation method, the splitting yield is high, the purity of a split product is high, the cost is low and environmental pollution is low.
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Paragraph 0059; 0060
(2017/09/05)
PROCESS FOR THE PREPARATION OF CLOMIPHENE
An improved process for the preparation of the active pharmaceutical ingredient Clomiphene and, in particular, trans-Clomiphene, using acetic acid or trifluoroacetic acid is disclosed.