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Santos (4-5) blew his sixth save of the season.
"It's a shame," White Sox manager Ozzie Guillen said. "(Axelrod is) pitching very well and all of a sudden we just blew it for him. Very nice day, you see this kid having success in his first time in the big leagues and all of a sudden, poof, another bad day for the White Sox."
Miguel Cabrera singled, doubled and scored a run for Detroit.
Alexei Ramirez laced a two-run double and Paul Konerko added a two-run single during Chicago's four-run second. Konerko reached 100 RBIs for the sixth time in his career.
Tigers starter Brad Penny allowed five runs -- one earned -- and eight hits over six innings. Phil Coke (3-9) threw a scoreless ninth for the win.
Ramirez doubled, singled, walked and scored a run. Alejandro De Aza doubled, reached base four times, scored two runs and stole a base for Chicago.
The 26-year-old Axelrod was starting in place of Jake Peavy, who was shut down for the remainder of the season. He appeared to be in line for the win until the ninth, when Leyland's parade of pinch-hitters pulled out another win.
"You're starting with a kid that just came from, what's the league, the independent league and he shut them down and all of a sudden these big league pitchers couldn't stop them," Ozzie Guillen said. "Look at yourself in the mirror and see how big league you are. If they're happy the season's over, good. But every time you lose a game like that and you have a little bit of pride, you should be ashamed of yourself."
The mood couldn't have been more different in the other clubhouse.
"We're having a good time," Raburn said. "We're having fun going out and playing, just trying to enjoy the moment and keep going on."
NOTES: The Tigers can clinch the AL Central during their four-game series at Oakland this weekend. In Thursday's opener, Detroit will send Max Scherzer to the mound to face Brandon McCarthy. Scherzer has allowed just two runs in 14 innings this month. ... The White Sox travel to Kansas City for a four-games series. On Thursday, Chicago's Mark Buehrle will square off against fellow lefty Jeff Francis. Buehrle has allowed 14 runs in nine innings over his last two starts.
Copyright 2011 The Associated Press. All rights reserved. This material may not be published, broadcast, rewritten or redistributed.
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