Jews found themselves on the wrong side of several Castilian civil wars between the great strides of the 1200s and the ultimate final conquest. Add in the Black Plague misplaced blame and the fact that Christian banking did not come to Spain nearly as fast as it came to Northern Italy and other Catholic areas, meaning that Jews and usury were still synonymous in the 1400s, and you have a perfect brew for expulsions.
Reconquista ideology over time grew more and more ingrained with the nobility of Iberia. The more inactive the struggle was in terms of actual territory gained, the more virulent and intolerant it became.
Ultimately, if Iberia is completely ruled by Christians in the aftermath of the great advances of the 1200s, and no Moorish entity remains, I don't think intolerance will become official policy because it will simply be impossible in 1250. By 1450 and after 200 years of Castilian colonization of the south because of the border warfare that was constant, in addition to assimilation efforts, official intolerance once conquest was achieved was quite possible. The best thing for the Jews in Spain would have been for an earlier final conquest.