3-[4-(Trifluoromethoxy)phenyl]acrylic acid

Synthesis

GENERAL STEPS: A mixture of 5.00 g (3.80 mL, 26.3 mmol) of 4-trifluoromethoxybenzaldehyde, 3.10 g (30.0 mmol) of malonic acid, 0.26 g (3.0 mmol) of piperidine, and 15.0 mL of pyridine was heated to reflux until carbon dioxide gas ceased to be produced (approximately 3 hours). Upon completion of the reaction, the mixture was cooled to room temperature and subsequently poured into a mixture consisting of 50 g of ice and 15 mL of 6N HCl. The precipitated solid was separated by filtration, washed with water and dried to give 5.20 g (85% yield) of 3-(4-trifluoromethoxyphenyl)acrylic acid. The product was characterized by 1H-NMR (400 MHz, D6-DMSO): δ = 6.57 (d, 1H, 2-H), 7.40 (d, 2H, 3'-/5'-H), 7.62 (d, 1H, 3-H), 7.84 (d, 2H, 2'-/6'-H), 12.5 (br, 1H, COOH).

References

[1] Patent: WO2004/85434, 2004, A1. Location in patent: Page 15
[2] Patent: US2005/209290, 2005, A1. Location in patent: Page/Page column 11
[3] Patent: US2005/267179, 2005, A1. Location in patent: Page/Page column 12
[4] Patent: US2007/259936, 2007, A1. Location in patent: Page/Page column 162