The invention discloses a preparation method of a cyclopofol intermediate cyclopropyl [2-hydroxy-3-(propyl-2-yl) phenyl]
ketone. 2-
isopropyl phenol is used as a starting material and reacts with a halogenating
reagent under the acidic condition to obtain a compound (A), the compound (A) reacts with a benzyl
reagent under the condition of an alkaline
reagent to generate a compound (B), the compound (B) and cyclopropanecarbonyl
chloride are subjected to a Friedel-Crafts
alkylation reaction under the condition of Lewis acid to obtain a compound (C), and the compound (C) and cyclopropanecarbonyl
chloride are subjected to a Friedel-Crafts
alkylation reaction under the condition of Lewis acid to obtain the compound. The compound (C) finally generates an intermediate compound (D) cyclopropyl [2-hydroxy-3-(propyl-2-yl) phenyl]
ketone under the condition of a hydrogenation reagent, the
molar yield can reach 85 +%, and the intermediate compound (D) and methyl triphenyl
phosphorus bromide are subjected to
ylide reaction to obtain 2-(1-cyclopropyl vinyl)-6-(propyl-2-yl)
phenol. Splitting (R)-(+)-1-phenylethyl
isocyanate to obtain {[(1R)-1-phenylethyl] amino} methanoic acid-6-[(1R)-1-cyclopropylethyl]-2-(propyl-2-yl) phenyl ester with a single configuration, wherein the {[(1R)-1-phenylethyl] amino} methanoic acid-6-[(1R)-1-cyclopropylethyl]-2-(propyl-2-yl) phenyl ester has a single structure; the purity of the finished cyclopofol finished product obtained through refining can reach 99.9%, the cost is low, operation is easy and convenient, and industrial production is easy.