All-atom molecular dynamics simulations are used to understand the structural and thermodynamic behavior of water in a biphasic system composed of a brine solution in contact with two different amine-based solvents, diisopropylamine (DiPA) and tripropylamine. As compared to the bulk brine solution, the biphasic system leads to significant salt aggregation and crystallization, and this behavior is observed over a relatively broad range of temperatures, from 278 to 343 K. In general, there are stronger hydrogen bond interactions between DiPA and water, leading to more favorable solvation and reduced diffusion rates. Detailed analysis of the solvation behavior is provided by using thermodynamic integration to calculate the free energy of water solvation in different brine and solvent mixtures. This also indicates a stronger interaction of water with the DiPA solvent, and this occurs mainly via interactions of the oxygen atoms in water with the nitrogen atoms of the solvent molecules. Overall, the structural and thermodynamic analyses in this study provide a better molecular-level understanding of solvent-based desalination of high-salinity brines. © 2021 American Chemical Society.