3-(4-Chloro-2-methylphenyl)benzoic acid synthesis

Yield:916220-05-8 12 g

Reaction Conditions:

with palladium 10% on activated carbon;sodium carbonate in water;isopropyl alcohol at 80;Inert atmosphere;

Steps:

4'-Chloro-2'-methyl-biphenyl-3-carboxylic acid (T2).

To a mixture of 3-iodobenzoic acid T1 (11.9 g, 48 mmol), 4-chloro-2-methylphenylboronic acid (9.8 g, 57.7 mmol) and sodium carbonate (6.1 g, 57.7 mmol) under nitrogen atmosphere, was added i-PrOH-water (1/1, 180mL) followed by 10% Pd-C (2 g, 19.2 mmol) with caution. The reaction mixture was heated at 80 °C under nitrogen overnight. The catalyst was removed by filtration, and the filtered catalyst was washed with EtOH (60 mL). Most of organic solvent was removed under reduced pressure. The resulting aqueous residue was treated with 2N HCl (aq) to bring the pH < 2. The resulting mixture was extracted with EtOAc (2 x 100 mL). The combined organic extracts were washed with water and saturated brine, dried over Na₂SO₄, filtered and concentrated under reduced pressure. Compound T2 was obtained as white solid (12 g), which was used directly in the next step. MS ESI (neg.) m/e: 245 (M-H).

References:

Ma, Zhihua;Lin, Daniel C.-H.;Sharma, Rajiv;Liu, Jinqian;Zhu, Liusheng;Li, An-Rong;Kohn, Todd;Wang, Yingcai;Liu, Jiwen;Bartberger, Michael D.;Medina, Julio C.;Zhuang, Run;Li, Frank;Zhang, Jane;Luo, Jian;Wong, Simon;Tonn, George R.;Houze, Jonathan B. [Bioorganic and Medicinal Chemistry Letters,2016,vol. 26,# 1,p. 15 - 20] Location in patent:supporting information