Tottenham had been linked with re-signing goalkeeper on a free transfer.
Lopez spent last season on loan at Tottenham but did not play a first team game.
He is a Spain under-21 international and has featured regularly for Espanyol this season.
Spurs rated him but were unwilling to meet Espanyol's asking price for the stopper last summer.
It had appeared possible Spurs chairman Daniel Levy was considering a masterstroke, having declined the chance to pay up, he could have engineered a move for Lopez on a free transfer this summer.
Ex-Espanyol boss Sergio Gonzalez told Tutto Mercato Web earlier this year that he believed Lopez could make a return to Tottenham on a free.
This now appears to be off the table with a switch to Real Betis imminent. It is claimed he has agreed a contract until 2023.
Betis are currently five places higher in La Liga than Lopez's current side Espanyol.
Tottenham's back-up goalkeeping position still has an uncertain future, with second choice Michel Vorm's contract expiring at the end of this season.