合成路线1

3,4,5-Trifluorobenzaldehyde (I) is converted into oxime (II) upon treatment with hydroxylamine in aqueous EtOH. Subsequent oxidation of oxime (II) with N-chlorosuccimide produces the hydroximinoyl chloride (III). In situ conversion of (III) to the corresponding nitrile oxide, followed by cycloaddition with N-allyl acetamide (IV) generates the racemic isoxazoline (V). After resolution of (V) by means of chiral HPLC, displacement of the para-fluoride group with piperazine in hot DMSO furnishes (VI). Acylation of piperazine (VI) by means of acetoxyacetyl chloride (VII) gives rise to amide (VIII). Finally, methanolysis of the acetoxy group of (VIII) in the presence of K2CO3 leads to the target hydroxyacetylpiperazine derivative. (1,2)