ContentFilm International has international sales rights, with CAA handling North America. Rachel Rothman, Tucker Tooley and Dan Keston are producing.
The coming-of-age story, written by Will Aldis, follows an 18-year-old boy who has led a sheltered life due to a serious heart condition. He then meets an alcoholic ex-stripper, played by Hayek, and decides to embrace life. Meanwhile, she mistakes him for a recovering alcoholic and he has to play up the new persona.
Shooting will start in Los Angeles in July, with DoP James Whitaker (Thank You For Smoking, The Cooler) on board.
Tooley said: 'Bill is such a dynamic force. Rachel, Dan and I feel very lucky that we can be a part of his directorial debut and that he shares our vision,' said Tooley. 'Will Aldis' script is so unique and compelling, we couldn't be happier to have Bill leading the charge.'
ContentFilm head Jamie Carmichael added: 'Having worked with William H Macy on Thank You For Smoking, The Cooler - and even on Transamerica where he was an executive producer - we feel that he belongs to us! So we just had to have his directorial debut.'
ContentFilm's EFM slate also includes action horror film Outpost, Fred Schepisi's war epic Last Man, and Peter Greenaway's Rembrandt biopic Nightwatching.