Two synthetic methods have been reported for the title compound. Coupling of aryl triflate (I) with thiomorpholine (II) affords the N-aryl thiomorpholine (III). Reduction of the nitroaryl group of (III) by catalytic hydrogenation in the presence of Raney nickel furnishes aniline (IV). This is then condensed with benzyl chloroformate under Schotten-Baumann conditions, yielding carbamate (V). Reaction of carbamate (V) with (S)-N-(2-acetoxy-3-chloropropyl)acetamide (VI) in the presence of lithium tert-butoxide and MeOH leads to the (S)-oxazolidine (VII). Finally, oxidation of the thiomorpholine sulfide group of (VII) with N-methylmorpholine-N-oxide in the presence of a catalytic amount of OsO4 gives rise to the title sulfone compound.
In an improved procedure, conjugate addition of divinyl sulfone (II) to 2,6-difluoroaniline (I) in the presence of AlCl3 leads to the N-aryl thiomorpholine sulfone (III). Aromatic nitration of (III) with fuming HNO3 in AcOH affords (IV). The nitroaryl derivative (IV) is then reduced to aniline (V) by catalytic hydrogenation over Raney Ni. Condensation of aniline (V) with isobutyl chloroformate furnishes carbamate (VI). This is finally cyclized with (S)-N-(2-acetoxy-3-chloropropyl)acetamide (VII) to generate the target oxazolidinone compound.