合成路线1

The intermediate (II) can be obtained as follows: 2) The reaction of 2,4-difluorophenacyl chloride (XII) with sodium acetate and NaI in DMF gives the acetoxy derivative (XIII), which is treated with methyltriphenylphosphonium bromide and sodium bis(trimethylsilyl)amide in THF yielding 2-(2,4-difluorophenyl)-2-propen-1-ol acetate (XIV). The saponification of (XIV) with KOH in water affords the unsaturated alcohol (XV), which is regioselectively epoxidized with titanium tetraisopropoxide, tert-butyl hydroperoxide and L-(+)-tartaric acid diethyl ester giving (S)-(-)-[2-(2,4-difluorophenyl)oxiran-2-yl]methanol (XVI). The condensation of epoxide (XVI) with 1,2,4-triazole (XVII) by means of NaH in DMF yields (R)-(-)-2-(2,4-difluorophenyl)-3-(1,2,4-triazol-1-yl)propane-1,2-diol (XVIII), which is treated with methanesulfonyl chloride and triethylamine affording the corresponding mesyl ester (XIX). Cyclization of (XIX) with NaOH in DMF affords the corresponding epoxide (XX), which is condensed with diethyl malonate (XXI) by means of NaH in DMSO giving 5(R)-(2,4-difluorophenyl)-2-oxo-5-(1,2,4-triazol-1-ylmethyl) tetrahydrofuran-3-carboxylic acid ethyl ester (XXII). The reduction of (XXII) with NaBH4 in ethanol yields the 4(R)-(2,4-difluorophenyl)-2-(hydroxymethyl)-5-(1,2,4-triazol-1-yl)penta n-1,4-diol (XXIII), which is selectively esterified with p-toluenesulfonyl chloride and dimethylaminopyridine/triethylamine to primary monosulfonate (XXIV). Finally, this compound is cyclized to (II) by means of NaH in refluxing toluene.