Witherspoon had been in the mix for "The Intern," but decided her schedule prohibited her involvement, Variety reported, citing sources it did not identify.
Warner Bros. was considering approaching Kristen Wiig about the role Witherspoon abandoned, sources said.
Witherspoon has also been busy clearing her decks in the real estate market. The Los Angeles Times said Saturday the Oscar-winning actress recently sold her getaway house in Ojai for nearly $5 million.
The so-called Libbey Ranch is a landmark in the secluded desert. It was built in 1923 by Wallace Neff, the influential architect who pioneered the "California" style of home design.
Witherspoon bought the nine-bedroom estate for $5.8 million in 2008, the peak of the California real estate boom.