Do NOT use a flammable replacement refrigerant in ANY system originally designed for R22. There are some hydrocarbon (propane) based replacement refrigerants sold online. They are NOT EPA approved and represent an explosive hazard when charged into a system that was not designed for flammable refrigerant.
Do NOT add ANY replacement refrigerant on top of an existing R22 charge. This is an EPA violation. You are essentially creating a “new” refrigerant which has not been tested or approved. There are NO replacement refrigerants which are legal to add in on top of an existing R22 charge. You must first remove ALL of the R22 when doing a conversion.
Do NOT use ANY 400 series refrigerant in a flooded system. Even refrigerants which are advertised to work in systems with mineral oil will still separate in the flooded portions of the system because they are not truly miscible. There is a difference between miscibility and solubility, but that is the subject for another whole article.
Do NOT use ANY replacement refrigerants in ANY system using an electronic expansion valve. This would primarily be older R22 minisplits, multisplits, and VRF systems. Trane hyperion heat pumps can sometimes have an R22 charge. In that specific case, the indoor air handler is designed for both R22 or R410A, so switching to R410A and changing the refrigerant dip switch solves that problem for the indoor air handler. Unfortunately, you will still have to replace the outdoor unit with one designed for R410A.
Do NOT use ANY 400 series replacement refrigerant in systems which were originally designed for R22 and have Trane 3D Scroll compressors. The lubrication system that specific compressor design uses does not work well with HFC refrigerants, including ones advertised as being compatible with mineral oil.
This all come down to one main strategy for replacing R22 in most older systems: it is generally best to replace the whole system. Not only does this avoid application problems, it usually provides a significant efficiency upgrade as well.