Protesters gathered near Monroe and State streets in the Loop about 5 p.m., protesting the president's visit.
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The president was in the city for about four hours as he attended the fundraiser at the Palmer House Hilton, his second in the past month.
A line of police blocked protesters from accessing the entrance to the hotel.
The pro-Palestinian demonstrators are critical of the president's support of Israel, in particular, at this moment, with an Israeli invasion of Rafah possibly imminent.
They stopped after marching through downtown, blocking traffic and spreading their message with loudspeakers. They first gathered for a rally near Michigan Avenue and Ida B. Wells Drive.
"Him and all of those ultra-rich millionaires and billionaires who are supporting him at this fundraiser who are also complicit in the genocide absolutely can hear us," said Hatem Abudayyeh with Chicago Coalition for Justice in Palestine.
Earlier in Wisconsin Biden spoke to CNN and acknowledged the dozens of college encampments that have formed.
"There's a legitimate right to free speech and protest. There's a legitimate to right to do that, and they have a right to do that. There's not a legitimate right to use hate speech," Biden said.
Biden said for the first time he would halt some shipments of American weapons to Israel if there's a major invasion of the city of Rafah.
"I think it's clearly too little, too late, but we also take credit for the fact that there has been a little bit of a shift in policy," Abudayyeh said.
President Biden arrived in Chicago a little after 3:30 p.m., stepping off Air Force One at O'Hare.
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From there, he took a helicopter to an area near Soldier Field, and then took a motorcade from there to the Loop, where he arrived for that fundraiser around 4:30 p.m.
The demonstrators are vowing to continue protesting the president's visits. That includes, of course, the Democratic National Convention this summer, where they're expecting tens of thousands to take to the streets.
Biden announces new Microsoft AI facility at site of failed Trump factory in Wisconsin
Earlier in the day Wednesday, Biden announced a $3.3 billion investment in Wisconsin.
President Biden announces new AI hub in WI before Chicago visit
Biden said the money will help create jobs as Microsoft builds a new artificial intelligence facility.
In 2018, then-President Donald Trump broke ground at the same site in Racine on what was supposed to be an electronics factory for Taiwan's Foxconn.
READ ALSO | Microsoft to build AI hub, train people how to best use artificial intelligence
President Joe Biden announces new Microsoft AI hub in WI ahead of Chicago visit
Trump had promised 13,000 jobs, calling the project the "Eighth Wonder of the World," as he used a golden shovel to break ground.
Construction equipment is now leveling land to build the data center.
"They dug a hole with those golden shovels, and then they fell into it," Biden said Wednesday.
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FoxConn never panned out, which was something President Biden drove home, as he trolled Trump during his stop in Wisconsin.
"FoxConn turned about to be just that, a con -- go figure," Biden said.
Biden joined Microsoft President Brad Smith to announce the data center that will be one of Microsoft's largest in the world. Unlike FoxConn, Smith said his company under-promises and over-delivers.
"We are going to be building one of the world's most advanced AI centers that you will see anywhere," Smith said.
Microsoft said just building the center will create over 2,000 union jobs. There will also be thousands of jobs once the project is complete. Some local union residents said Wednesday's announcement should be enough to get undecided voters to vote for Biden.
"Absolutely, there are going to be a lot of workers at Microsoft. Everybody is successful over there," Racine resident Meekma said.
Besides union voters, President Biden is making a big push to get more Black voters.
After the Microsoft event, he stopped at a small Racine community center, where he received a standing ovation.
Wisconsin is such an important state for the Biden/Harris ticket. Wednesday's visit by the president is one of many there.
Vice President Kamala Harris will be making yet another stop in Milwaukee on May 16 to tout the administration's economic agenda.
"Whatever your politics may be, you got to look at the people who are the helping hand," Mount Pleasant, Wisconsin resident Lyle Tryba said.