Uses
3’-Amino-2’-Hydroxy-[1,1’]Biphenyl-3-carboxylic Acid is used in the synthesis of monoethanolamine salts. A hydrazine cleavage product from Eltrombopag (E508000), an agonist of the Thrombopoietin (Tpo) receptor, used as treatment for thrombocytopenia
Synthesis
The general procedure for the synthesis of 3'-amino-2'-hydroxy-[1,1'-biphenyl]-3-carboxylic acid from 5'-chloro-2'-hydroxy-3'-nitro-[1,1'-biphenyl]-3-carboxylic acid is as follows: 5'-chloro-2'-hydroxy-3'-nitro-biphenyl-3-carboxylic acid (Compound 2b) (5.0 g) was dissolved in a methanol (MeOH) (300 mL) and triethylamine (Et3N) (4.75 mL) in a solvent mixture. A palladium/carbon (Pd/C) catalyst (0.5 g) was added to the solution, followed by hydrogenation at room temperature and 10 bar hydrogen pressure for 21 hours. Upon completion of the reaction, the catalyst was removed by filtration and the filtrate was concentrated to dryness. The obtained residue was dissolved in water (40 mL) and the pH was adjusted to 5.5 by dropwise addition of 0.5 M hydrochloric acid (HCl). the resulting suspension was stirred at room temperature for 30 min, followed by filtration. The collected solid product was washed with water (2 x 10 mL) and finally dried at 50 °C/50 mbar to afford the target product 3'-amino-2'-hydroxy-[1,1'-biphenyl]-3-carboxylic acid (BPCA) (3.4 g; yield 86.7%; HPLC purity 97.9%).
References
[1] Patent: WO2013/49605, 2013, A1. Location in patent: Paragraph 0058
