Should be possible, I don't think SEP Upgrade/Windows Updates are applied at the same stage during the boot (some Microsoft Updates are even partially installed before reboot).
However, any additional changes might have side effects, depending on files modified by 3rd party (by Windows Updates in your case). So I would basically recommend to perform a first reboot during your scheduled maintenance/down-time to apply Windows Updates, then upgrade SEP to 12.1 and reboot once more to get it installed.