NEW YORK, USA (AP) — So far in his first Grand Slam title defence, Andy Murray needed to beat players who are ranked 47th, 49th, 65th and 81st.

He’s well aware things probably will get a tad tougher the rest of the way at the US Open, starting with number nine Stanlisas Wawrinka in the quarter-finals.

“Hopefully I’ll start playing a little bit better from now on. I mean, sometimes the first week of a Slam, I’ve played very well. Sometimes you maybe feel like there’s a little bit something to lose,” said Murray, who is 30-2 over the past five major tournaments.

“I’m in the quarter-finals of a Slam. It’s not an easy thing to do, and the matches are going to get tougher,” he said. “I’ll have to up my game.”

In a 6-7 (5), 6-1, 6-4, 6-4 fourth-round victory over Denis Istomin of Uzbekistan on a windy Tuesday night, Murray found reasons to yell at himself for mistakes.

He faltered late in the first set, dropping four points in a row. He also flubbed what should have been a simple volley after Istomin’s between-the-legs shot late in the second. There was more shakiness from Murray in the third set, in which he went up a break, only to lose serve to make it 3-all. But he broke right back for a 4-3 edge, and was back on his way.

Murray’s back felt a bit stiff, he said afterward, owing to the cold, windy conditions.

“I wanted to just try and get through the match,” he said. “With the way the third set ended up going, I was just very happy to get it done.”

Murray leads the head-to-head series against Wawrinka 8-5, but they’ve split their two previous meetings on the US Open’s hard courts: Murray won in 2008, and Wawrinka won two years later. Wawrinka won their only match this season, 6-1, 6-2 on red clay at Monte Carlo in April.

“To beat him,” Wawrinka said, “I need to play my best tennis, that’s for sure”.

If Murray can get past Wawrinka, who eliminated number five Tomas Berdych 3-6, 6-1, 7-6 (6), 6-2, Djokovic might very well be waiting in the semi-finals. The top-seeded Djokovic, whose six major titles include the 2011 US Open, has yet to drop a set and won 45 of 53 service points while beating 43rd-ranked Marcel Granollers 6-3, 6-0, 6-0 Tuesday.

In his 18th consecutive Grand Slam quarter-final, which comes today, Djokovic will face 21st-seeded Mikhail Youzhny.

The men’s quarter-finals yesterday were number two Rafael Nadal against number 19 Tommy Robredo at night, and number four David Ferrer against number eight Richard Gasquet in the afternoon. The women’s quarter-finals on yesterday’s schedule were number two Victoria Azarenka vs Daniela Hantuchova at night, and number 10 Roberta Vinci against Flavia Pennetta in the afternoon.

All eight men’s quarter-finalists are from Europe: Serbia’s Djokovic, Britain’s Murray, Switzerland’s Wawrinka, Russia’s Youzhny on one half of the draw, and Spain’s Nadal, Ferrer and Robredo, along with France’s Gasquet on the other half.

One women’s semi-final matchup was set Tuesday: Number one Serena Williams of the United States, the defending champion, against number five Li Na of China, who won the 2011 French Open.

Williams shut out 18th-seeded Carla Suarez Navarro of Spain 6-0, 6-0, the first “double bagel” in a quarter-final at Flushing Meadows since 1989, when 18-time major title winner Martina Navratilova did it to Manuela Maleeva.

“When you play against Serena,” Suarez Navarro said, “you know these things can happen”.

Williams won 53 of 71 points and dominated pretty much every statistical category. The first set took all of 19 minutes. The second was slower, lasting 33 minutes, but no less lopsided.

Williams was asked whether she’d describe her performance as close to flawless.

“Of course not,” the 16-time major champion said with a laugh. “I played good, though. I played really good. I was just more focused than anything. You know, I like to believe there is room for improvement.”

Through five matches, Williams has dropped a total of 13 games. Going back to the start of Wimbledon last year, the 31-year-old American is 96-5 with 13 trophies, including from three of the past five Grand Slam tournaments plus the London Olympics.

“She’s the best player in the sport,” Suarez Navarro said. “When you look at the draw, you don’t want to see Serena there.”

Li needed nearly 2 1/2 hours to get past 24th-seeded Ekaterina Makarova of Russia 6-4, 6-7 (5), 6-2 in the quarter-finals.

Heading into their meeting Friday, Li is 1-8 against Williams.

“Tough, tough opponent,” Li said.