The first attempt, commanded by Ruy López de Villalobos, left Mexico at the start of November 1542 and arrived off the eastern coast of Mindanao at the end of February 1543.
After another failed attempt to send a ship back across the Pacific, notions about Portuguese indifference came unstuck.
A delegation arrived with a letter from the Portuguese governor in the Moluccas, demanding an explanation for their presence in Portuguese territory. Villalobos' response claimed they were not trespassing at all.
While calculating longitude was an inexact science at the time, that seems to be bending things a tad too far. The Spaniards' position on the southern tip of Central Mindanao was west of the meridian passing through Ternate and Tidore.
Two attempts to cross back to Mexico failed. Unfavourable winds forced the second back to Tidore, where the Portuguese authorities placed them under arrest.
López de Villalobos died in a prison cell on Amboina on 4 April 1546, most likely due to a tropical fever. The Spanish version of events ascribes his death to dark melancholia and "a broken heart".
However, he did receive the last rites from St Francis Xavier. One hundred and seventeen of his crew survived. Thirty chose to remain with The Portuguese in the East. The rest headed home via Malacca and Lisbon.
Wars in Europe and political considerations meant it was almost twenty years before another serious effort established a permanent settlement in the Philippines.
When a gout-ridden Charles I abdicated the Spanish throne in January 1556, his successor, Philip II, was in the Netherlands.