Synthesis and structural studies of a novel scaffold for drug discovery: a 4,5-dihydro-3H-spiro[1,5-benzoxazepine-2,4′-piperidine]

We describe the three-step synthesis of a novel 4,5-dihydro-3H-spiro[1,5-benzoxazepine-2,4′-piperidine] scaffold from ortho-hydroxyacetophenone and N-benzylpiperidone. The structure of one disubstituted derivative, studied by NOESY NMR in an aqueous medium and X-ray diffraction, demonstrates that this scaffold presents side chains in a well-defined orientation. The Boc protected derivative represents a key intermediate for the combinatorial synthesis of drug-like molecules.