I have a 4 ton central heating and a/c. My bathroom was remodeled and now is 66 sf. My existing flex duct to the bath is 7" DIA.
Can I use a 12x4 supply boot with a 7" duct, or do I have to change the duct size?
How can I calculate the size of a supply boot according to duct size?

I wouldn't worry about this 66 so ft, and 12 x 4? a 7 inch duct is huge for any bathroom, just be sure that the flex ducting is taught and without sags or bends, they must be taut and straight.