The EHLO Blog post explaining support for .NET Framework 4.6.1 and all the other new Cumulative Update goodness can be read in the article, Released: June 2016 Quarterly Exchange Updates.
If you previously blocked .NET Framework 4.6.1 installation via the registry you'll need to remove that block by removing the "BlockNetFramework461" DWORD value from the registry in HKEY_LOCAL_MACHINE\SOFTWARE\Microsoft\NET Framework Setup\NDP\WU.
The recommended order of operations for installation is:
- Install Exchange Server 2016 CU2 or Exchange Server 2013 CU13 on your Exchange server. Restart.
- Remove the block for .NET Framework 4.6.1 from Windows Update (see key above).
- Download and install .NET Framework 4.6.1 from Windows Update. Restart.
- Note: The Exchange assemblies will recompile when the server starts back up. This will take several minutes and Exchange performance will suck during this time. I recommend downloading and running the NET Framework optimization speed up script from the .NET Blog. to make this process run faster.
- Download and install the appropriate post-release fixes for the .NET Framework:
- Windows Server 2008/2008 R2 – KB3146716
- Windows Server 2012 – KB3146714
- Windows Server 2012 R2 – KB3146715
- Restart and run the NET Framework optimization speed up script again.
- Personally, I would restart again just to make sure everything starts up correctly.