4-(4-n-Butylphenyl)benzoic acid

Uses

4''-Butylbiphenyl-4-carboxylic Acid is an intermediate used in the preparation of biphenylcarboxylates used as RARβ2 receptor agonist.

Synthesis

General Method 13: Synthesis of biaryl or aryl-heteroaryl carboxylic acids from 1-bromo-4-butylbenzene and arylboronic or heteroarylboronic acids by Suzuki coupling reaction. This method is specifically applied to the synthesis of 4-n-butylbiphenyl-4'-carboxylic acids. A mixture of methyl 4-(4-butylphenyl)benzoate (89.0 g, 0.332 mol) and NaOH (26.6 g, 0.664 mol) in THF/H2O (500 mL/100 mL) mixed solvent was heated to reflux and reacted overnight. The progress of the reaction was monitored by thin layer chromatography (TLC) and after confirming the completion of the reaction, THF was removed by distillation under reduced pressure.The residue was acidified to pH 3-4 with 2N HCl solution.The resulting mixture was filtered and the filter cake was washed with deionized water and dried to give 4-(4-butylphenyl)benzoic acid (60.0 g, yield: 71.1%) as white solid. The mass spectrum (ESI) showed m/z 255.0 ([M+H]+).

References

[1] Patent: WO2013/123456, 2013, A1. Location in patent: Paragraph 00269; 00271
[2] Patent: WO2017/84629, 2017, A1. Location in patent: Paragraph 00341
[3] Patent: WO2017/84630, 2017, A1. Location in patent: Paragraph 00444
[4] Patent: US2013/217619, 2013, A1. Location in patent: Page/Page column