The influence of an F-atom in the side chain of benzo[7]annulen-7-amines on the affinity towards GluN2B subunit containing NMDA receptors and the selectivity over related receptors was investigated. The synthesis of <b>5a</b> and <b>5b</b> was performed by reductive amination of the ketone <b>6</b> with primary alkanamines <b>14a</b> and <b>14b</b> bearing an F-atom in β-position. The GluN2B affinities of non-fluorinated and fluorinated ligands <b>4</b> and <b>5</b> are almost identical. The low impact of the F-atom on GluN2B affinity was unexpected, as it influences several chemical and physicochemical properties of the ligands. However, introduction of the F-atom led to reduced selectivity over <i>σ</i> receptors. Whereas <b>5a</b> and <b>5b</b> display still a 2-3-fold preference for GluN2B over <i>σ</i><sub>1</sub> receptors, they show almost the same affinity to GluN2B and <i>σ</i><sub>2</sub> receptors.