Orange County Fire said the crash occurred near Willow Street shortly after 1 a.m. and left two people hurt.
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Hazmat crews were called to the scene after a large oil and gas leak was reported following the crash.
The driver of the semi-truck was OK and did want medical treatment, while one patient in a BMW was transported to a trauma center, according to authorities.
Video from the scene showed the BMW vehicle with extensive front-end damage and the semi-truck on its side.
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It appeared the semi-truck was carrying a carnival ride in the back of the trailer.
All southbound lanes were shut down, and California Highway Patrol said traffic was being diverted off at Spring Street.
Lanes began to reopen around 9 a.m.