Facile synthesis of 7-10 membered rings by intramolecular condensation using dialkylcarbonate as solvent

A convenient large-scalable synthesis of 1-benzazepines 19 as an important intermediate of CCR5 antagonist, oral HIV-1 therapy, was established. The anilination of o-halogenobenzaldehyde 9 with alkylamino-acid 16 gave o-formylaniline-acid 17. Compound 17 was esterified followed by the improved reaction using the combination of alcoholate and dialkyl carbonate in one-pot, to easily produce 19. Namely, these new processes afforded the desired product 19 in only two steps from the starting materials, as compared with the previous 10 steps. Moreover, these convenient methodologies were applied to other heterocycles to give 8-10 membered rings, such as 1-benzazocine, 1-benzazonine, and 1-benzazecine.