Solid phase synthesis of 3,5-disubstituted oxazolidin-2-ones

A versatile method for the solid phase synthesis of oxazolidin-2-ones is described. A resin bound phenolic group was treated with (±)-epichlorohydrin followed by opening of the epoxide ring with sodium azide. The resulting 1-azido-3-aryloxypropan-2-ol was treated with p-nitrophenylchloroformate and subsequent Staudingerʹs cyclization using PPh3 yielded a 5-substituted oxazolidinone. Finally, additional diversity at position 3 was introduced by treating the 5-substituted oxazolidinone with an alkyl halide in the presence of NaH to give the desired compound in high yield and purity.