[4'-(pentyloxy)[1,1'-biphenyl]-4-yl]boronic acid

Uses

4-Pentoxybiphenylboronic acid can be used as a pharmaceutical synthesis intermediate, such as in the preparation of anidulafungin. Anidulafungin is a derivative of amphotericin B, a third-generation semi-synthetic echinocandin antifungal drug developed by Vicuron Pharmaceuticals in the United States, marketed under the brand name Eraxis, and approved for marketing in the United States in 2006. Compared with other echinocandin antifungals, anidulafungin has a larger volume of distribution and a broader spectrum of antibacterial activity.

Synthesis

General method: n-Butyl lithium (n-BuLi, 2.5 M, 7.4 mL, 18 mmol) was slowly added dropwise to a solution of methyl tertiary butyl ether (MTBE, 50 mL) of 4-bromo-4'-(pentyloxy)biphenyl (4.5 g, 13 mmol) at -20 °C under nitrogen protection. After stirring the reaction mixture for 2 h, it was cooled to -60 °C and tetrahydrofuran (THF, 6 mL) was added. Subsequently, a solution of triisopropoxyborane ((i-PrO)3B, 6.1 mL, 26 mmol) in methyl tert-butyl ether (MTBE, 8 mL) was slowly added dropwise to the reaction mixture and stirring was continued for 1 hour. The reaction mixture was gradually warmed to room temperature and stirred overnight. The reaction mixture was treated with 2M hydrochloric acid (HCl, 50 mL) for 10 minutes. The organic layer was separated and concentrated under reduced pressure to remove the solvent. Hexane (40 mL) was added to the residue and stirred for 10 minutes. After filtration, the filter cake was washed with a solvent mixture of hexane-methyl tert-butyl ether (8:1) to afford (4'-(pentyloxy)-[1,1'-biphenyl]-4-yl)boronic acid (15c, 3.7 g, 91.4% yield) as a white solid.

References

[1] European Journal of Medicinal Chemistry, 2012, vol. 50, p. 196 - 208
[2] Molecular Crystals and Liquid Crystals Science and Technology Section A: Molecular Crystals and Liquid Crystals, 2000, vol. 339, p. 145 - 158