# Synthesis of trans-2,5-Disubstituted Tetrahydro-1-benzazepines via Nucleophilic Ring Opening of Selectively Quaternized N,N‑Acetals

## TL;DR

Researchers developed a simple two-step method to make a type of chemical compound that can be used to create drugs like mozavaptan for treating low sodium levels.

## Contribution

A new one-pot, two-step method for synthesizing trans-2,5-disubstituted tetrahydro-1-benzazepines via quaternization and nucleophilic ring opening.

## Key findings

- The method uses readily available aryl-fused N,N-acetals and is compatible with a wide range of nucleophiles.
- The approach was successfully used to synthesize mozavaptan, a drug for hyponatremia.
- The process is operationally simple and provides an effective route for compound synthesis.

## Abstract

A one-pot, two-step
sequence involving a regiospecific quaternization
of readily available aryl-fused N,N-acetals followed by a stereospecific nucleophilic ring opening has
been developed. A wide range of nucleophiles have been shown to be
compatible with this reaction sequence. This operationally simple
methodology provides an effective route for the synthesis of a variety
of trans-2,5-disubstituted tetrahydroarylazepines.
In a demonstration of the utility of this reaction sequence, mozavaptan,
a compound that is beneficial in the treatment of hyponatremia, has
been efficiently prepared.