Synthesis
The general procedure for the synthesis of 3-(4-iodophenyl)propionic acid from hydrogenated cinnamic acid is as follows:
1. Preparation of Intermediate 1: A mixture of H2SO4 (1.25 mL), water (12.5 mL) and AcOH (25 mL) was added to a 250 mL flask. Subsequently 3-phenylpropionic acid (3.00 g, 20.0 mmol), iodine (1.40 g, 5.5 mmol) and KIO3 (0.98 g, 4.6 mmol) were added.
2. the reaction mixture was heated to reflux and a solution of AcOH (25 mL) with iodine (1.40 g, 5.5 mmol) was added in portions, 5 mL at a time. the color of the solution gradually changed from purple to orange during the reaction.
3. After the reaction was carried out for 3 hours, when the color no longer changed, the reaction mixture was cooled to room temperature and the reaction was subsequently quenched with 1 M NaHSO3 solution.
4. Water was added to the reaction mixture and extracted with EtOAc. The organic phases were combined, washed with brine, dried over MgSO4 and concentrated in vacuum.
5. The crude product (4.15 g, 75% yield) containing a small amount of starting material and by-products was recrystallized by petroleum ether to give 1.83 g of pure white crystalline product (33% yield).
Rf value: 0.10 (EtOAc:hexane, 1:4);
1H NMR (CDCl3) δ 7.62-7.59 (m, 2H), 6.97-6.95 (m, 2H), 2.92-2.87 (t, 2H, J = 7.5 Hz), 2.68-2.63 (t, 2H, J = 7.5 Hz);
13C NMR (CDCl3) δ 178.5, 139.7, 137.6, 130.4, 91.6, 35.2, 30.0.
References
[1] Patent: WO2010/12650, 2010, A1. Location in patent: Page/Page column 38
[2] Chemistry - A European Journal, 2009, vol. 15, # 10, p. 2278 - 2288
[3] Journal of the American Chemical Society, 2009, vol. 131, # 47, p. 17500 - 17521
[4] European Journal of Organic Chemistry, 2015, vol. 2015, # 27, p. 5919 - 5924
[5] Patent: WO2016/201125, 2016, A1. Location in patent: Page/Page column 19
