Kohlschreiber, who won the tournament in 2007, 2012 and 2016, had to save a set point in the tiebreaker then earned the decisive break for a 5-4 lead in the second before serving out the match. The loss extended a recent slump for Khachanov, who has not won a single set since the Indian Wells tournament in March. He also lost his opening matches at Miami, Monte Carlo and Barcelona since then.
Kohlschreiber will next face Matteo Berrettini of Italy, who beat unseeded American Denis Kudla 7-5, 6-3. Kudla, who is ranked 82nd, had upset the fifth-seeded Kyle Edmund on Tuesday.
Also Thursday, the fourth-seeded Roberto Bautista Agut defeated German wild card Rudolf Molleker 6-4, 6-2 to set up a meeting with Guido Pella, who ousted Taro Daniel of Japan 6-1, 6-7 (7), 6-3.
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