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N-Methyl-D-aspartate (NMDA) receptors are ligand- and voltage-gated ion channels that are critical for synaptic plasticity, learning, and memory. These receptors are variously composed of GluN1, GluN2A–D, and GluN3A/B subunits. They are widely expressed in the central nervous system and are implicated in several neurological, neurodegenerative, and psychiatric disorders. The GluN2B subunit has garnered particular interest due to its high expression in the forebrain and spinal cord, role in pathophysiological processes, and potential as a therapeutic target. Consequently, there is continuing strong interest in developing radioligands for imaging brain NMDA receptors with positron emission tomography (PET). We report the synthesis of nineteen 3-alkylaryl derivatives of 7-methoxy-2,3,4,5-tetrahydro-1H-benzo[d]azepin-1-ol and some of their enantiomers as prospective GluN2B PET radioligands. The absolute configuration of one core ligand was determined with vibrational circular dichroism and infrared spectroscopy, allowing the determinations of the absolute configurations of enantiomers of other ligands derived from this parent ligand. The GluN2B binding pocket showed generally broad tolerance for alkyl tether chain length and for alterations of both bulk and substitution in the terminal aryl group. No relationship between GluN2B affinity and computed compound lipophilicity was observed. Enantiomers of two prepared ligands, L3 (NR2B-SMe) and L6 (NR2B-Me), have desirably strong affinity for GluN2B, moderate lipophilicity, and amenability for labeling with carbon-11 (t1/2 = 20.4 min). In subsequent and separate PET studies, [S-methyl-11C](S)-L3 and [C-methyl-11C](R)-L6 have shown strong specific binding to GluN2B in animal brain. Synthesis methods and other data from this study can guide and support the further development of candidate GluN2B PET radioligands for clinical applications.