A practical and stereoselective synthesis of (+/−)-trans-4-benzyloctahydropyrrolo[3,4-b][1,4]oxazine

trans-Octahydropyrrolo[3,4-b][1,4]oxazine is an important heterocycle within the pharmaceutical industry for the preparation of biologically active analogs, including the phase III drug, finafloxacin. A practical synthesis of the title compound (2) is described in eight steps and ca. 10% overall yield. The key synthetic step is the formation of the pyrrolo[3,4-b][1,4]oxazine core 20 via a one pot double N-alkylation of the corresponding bis-tosylate 18 with 4-nitrobenzenesulfonamide. Subsequent removal of the nosyl group occurred under mild conditions.