合成路线1

Condensation of 1,2-difluoro-4-nitrobenzene (I) with thiomorpholine (II) using DIEA in refluxing acetonitrile at 85 °C yields 4-(2-fluoro-4-nitrophenyl)thiomorpholine (III) , which is then reduced by means of either Na2S2O4 in THF , Fe in the presence of NH4Cl in refluxing H2O/EtOH/dioxane , or by catalytic hydrogenation over Raney-Ni in THF/H2O (1) or sulfided Pd/C in MeOH , providing 3-fluoro-4-thiomorpholin-4-ylaniline (IV) . Acylation of amine (IV) with benzyl chloroformate (V), optionally in the presence of DMA , in THF affords carbamate (VI) , which then cyclizes with (R)-(–)-glycidyl butyrate (VII) using BuLi in THF at –78 °C to produce the 5-(hydroxymethyl)-2-oxazolidinone derivative (VIII). Reaction of the primary alcohol (VIII) with MsCl using Et3N in CH2Cl2 or with TsCl in pyridine yields the corresponding mesylate (IXa) or tosylate (IXb) , respectively, which by substitution with NaN3 in DMF at 65-85 °C provides azide (X). Staudinger reduction of azide (X) with PPh3 in THF/H2O then yields the corresponding amine (XIa). Finally, amine (XIa) or its hydrochloride (XIb) are acylated with acetic anhydride (XII) in the presence of pyridine in CH2Cl2 or NaOH in H2O/MeOH/CH2Cl2 .