A little tip as the question has already been asked several times:
Do I also have to take the .NET Framework into account when installing Exchange Updates (CUs)?
Simple answer: Yes!
Here is the somewhat more detailed answer:
Unsupported NET Framework versions in conjunction with Exchange Server can be quite problematic, as has been shown in the past:
https://www.frankysweb.de/net-framework-4-6-1-nicht-auf-exchange-servern-installieren/
However, the NET Framework version must also be taken into account when updating older Exchange versions. Here is a small example:
Exchange CUs normally contain all patches from previous versions, so in theory it is perfectly possible to install an Exchange 2016 server with CU1 and update directly to CU5. It is therefore not necessary to first install CU2, then CU3, then CU4 and finally CU5.
So much for the theory, now for the practice:
Let's imagine an Exchange 2016 server with CU3 installed and NET Framework 4.5.2 on the server. In this case, for example, it is not possible to update directly to CU5. Background CU4 requires at least NET Framework 4.6.1, but this is not supported by CU3. This means that you must first update to CU4, then update NET Framework to version 4.6.2 and only then can you update to CU5.
Source: Exchange 2016 prerequisites
Same game for Exchange 2013:
If the Exchange Server has a patch level before CU15, it is not possible to update directly to CU16. In this case, CU15 must be installed first, then NET Framework must be updated and only then can CU16 be updated.
This type of NET Framework dependency can also be found in other constellations, as some Exchange CUs do not support the required NET Framework version of the more recent CUs. In this case, an older CU must first be updated so that the required NET version can be installed.
Currently, for example, it is still recommended not to install NET Framework 4.7 on Exchange servers:
You should therefore always take a look at the NET Framework version before installing Exchange CUs.
The currently supported .NET Framework versions can be found here:
Source: Exchange Server Supportability Matrix