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He’s 2-12 in tour matches against Djokovic, including 11 consecutive losses.

Other than the third set against Youzhny, when he got broken twice and made 16 unforced errors, six-time major champion Djokovic has looked solid all tournament. Djokovic lost to Murray in the 2012 final at Flushing Meadows, then again in this July’s final at the All England Club, and that duo appeared on course for a rematch in the semifinals this weekend, but Wawrinka put an end to that possibility.

It’s been quite a 14-month stretch for Murray.

He lost to Federer in the Wimbledon final last year, then returned to Centre Court four weeks later and beat the 17-time major champion to earn a gold medal for Britain at the London Olympics. After starting his career 0-4 in Grand Slam finals — his current coach, Ivan Lendl, is the only other man to do that — Murray finally won one in New York a year ago. And then, after a runner-up finish to Djokovic at the Australian Open in January, Murray became the first British man in 77 years to win Wimbledon.

That raised talk of knighthood at home and questions about whether he’d prefer to reach No. 1 in the rankings or add more major titles.

But before this U.S. Open began, Murray seemed amazed by how many off-court commitments a defending champion needs to deal with at Grand Slam time. Then, thanks to the vagaries of scheduling and weather, he didn’t play his first match until the third night of the tournament. He hardly looked at ease during a four-set, fourth-round win against a guy ranked 65th.

Didn’t get better against Wawrinka.

“It was a new experience for me and something that was good to go through,” Murray said, “and I will learn from that for next time.”

The unraveling began with Murray serving while behind 5-4 in the first set.

“Important game,” Murray said.

Troubled, perhaps, by swirling wind, not to mention Wawrinka, Murray kept missing the mark, especially with his forehand. Never a paragon of positive reinforcement during a match, he kept gesticulating and yelling and generally looking ill at ease.

The second set slipped away even faster, with Murray hanging his head after a forehand into the net closed a 12-point and three-game run for Wawrinka that made it 5-2. That was pretty much that.

“If I’m meant to win every Grand Slam I play or be in the final, it’s just very, very difficult just now,” said Murray, who packed up his gear and raced into his news conference so swiftly that Wawrinka was still conducting his on-court interview. “With the guys around us, it’s very challenging.”

For about a decade, men named Federer, Nadal, Djokovic and Murray have dominated the latter stages of major tournaments. That quartet won 33 of the past 34 Grand Slam titles, but two are gone from the field already.

“In tennis, as you know, if (you) are not Roger or Rafa and Djokovic or Andy now, you don’t win so many tournaments,” Wawrinka said, “and you always lose.”

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