If it appears that Exchange is down, OWA failed, ECP, Exchange shell, and all Outlook clients can not connect. Check the System log and if you are seeing a lot of 15021 HttpEvent errors with an error occurred while using SSL configuration for endpoint 0.0.0.0:444 as shown below.
Open up IIS Manager and check the backend website and looked at the SSL Binding. There was no certificate attached for some reason.
Reselect the same certificate that the front end is using and click ok.
Run a “iisreset” on the Exchange server and test exchange access again.