World number 16 Roberto Bautista Agut crashed out in the second round as the other favourites for the Generali Open battled through.
Bautista Agut lost the first set to Spanish compatriot Pablo Martinez in Kitzbuhel, Austria, and could not complete a comeback despite forcing a decider as he lost 6-4 6-7 (5-7) 7-5.
Top seed Casper Ruud, who won last week in Gstaad to claim his third ATP Tour crown of 2021 and fourth in total, came from 4-2 down in the first set to win 7-5 5-7 6-4 against Mario Vilella Martinez.
Third seed Filip Krajinovic survived a second-set scare to beat Carlos Taberner 6-3 2-6 6-4.
Arthur Rinderknech, who dispatched of fifth seed Federico Delbonis on Tuesday, awaits Krajinovic in the next round.
The other clash on Wednesday saw Sweden's Mikael Ymer cruise past home favourite Alexander Erler 6-2 6-3 to secure a quarter-final berth.
Ymer will now face the thankless task of challenging 22-year-old Ruud for a spot in the semi-finals.