合成路线1

The cyclization of 2-fluoro-3-oxopentanoic acid ethyl ester (I) with formamidine (II) by means of sodium methoxide in refluxing methanol gives 6-ethyl-5-fluoropyrimidin-4(3H)-one (III), which by reaction with refluxing POCl3 is converted into 4-chloro-6-ethyl-5-fluoropyrimidine (IV). The condensation of (IV) with 1-(2,4-difluorophenyl)-2-(1,2,4-triazol-1-yl)ethanone (V) by means of lithium diisopropylamide in THF yields two pairs of diastereomers (R*,S*)-3-(6-chloro-5-fluoropyrimidin-4-yl)-2-(2,4-difluorophenyl)-1-(1,2,4-triazol-1-yl)-2-butanol (VI) (racemic pair A) and the (R*,R*)-racemic pair B (VII). The reductive dechlorination of (VI) with H2 over Pd/C in ethanol affords the racemic pair (VIII), which is submitted to optical resolution with 1(S)-(+)-10-camphorsulfonic acid.