1) Build a box of solvent and equilibrate it.
2) Build the solute model, minimize in vacuum, possibly with restraints to preserve important structural features.
3) Combine systems, use DELETE with .AROUND. selection to remove solvent that overlaps the solute.
4) Minimize result, again probably with solute restraints.
There are examples in the Script Archive forum that can be adapted for the above steps using your specific system.