Acrobat DC

As Dov Isaacs said, you should try to merge PDFs into several groups and then combine them together.

Restarting the computer shouldn't make any difference whatsoever since Acrobat doesn't “remember” anything between subsequent executions of the software, regardless of whether the system has just been rebooted.

And contrary to what most users might believe, neither Acrobat nor any other applications use RAM as they did in the 1990s. MacOS and Windows are both virtual memory operating systems. Applications may request additional address space that temporarily uses RAM when necessary, but I doubt whether is any issue with running out of virtual memory.

What is true is that when you combine PDF files, it is not simply a matter of physically concatenating one file with another. A full optimization process occurs in which fonts are examined and subsets are reconciled and combined as possible to cut down on final PDF file size and to optimize subsequent access. The bigger and/or more complex the files are, the more complex and time-consuming this optimization process takes.

One thing you might try instead of sequentially combining files is to combine the first 5 files into one file, followed by the next five files into another file, etc. Then combine the resultant files together in small groups, ultimately ending up with the one, big, honk'in PDF file you are trying to achieve.