6-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)quinoxaline

Uses

Quinoxaline-6-boronic acid pinacol ester is a common reactant of a Suzuki coupling reaction that can be used:

• To prepare quinoxalin based PI3Kδ inhibitors.
• As a substrate in the Cu(II) catalyzed [¹¹C]-radiocyanation of arylboronic acids.
• To prepare 6-quinoxaline boronic acid, which is used as a substrate in the silver-mediated fluorination of boronic acids.

Synthesis

To a solution of 6-bromoquinoxaline (418 mg, 2.00 mmol, 1.00 eq.) in dioxane (10 mL) at 23 °C was sequentially added PdCl2(dppf)-CH2Cl2 (163 mg, 0.200 mmol, 0.100 eq.), bis(pinacolide)diboron (610 mg, 2.40 mmol, 1.20 eq.) and KOAc (392 mg, 4.00 mmol, 2.00 equiv). The reaction mixture was stirred at 90 °C for 1.5 h, subsequently cooled to 23 °C and concentrated in vacuum. The residue was dissolved with CH2Cl2 and filtered through a diatomaceous earth plug. The filtrate was concentrated under reduced pressure and purified by silica gel column chromatography with hexane/EtOAc (4:1, v/v) as eluent to give 500 mg of quinoxaline-6-boronic acid pinacol ester as a colorless solid (98% yield). Thin layer chromatography Rf = 0.45 (unfolding agent: hexane/EtOAc, 1:1, v/v). Nuclear magnetic resonance hydrogen spectrum (1H NMR, 500 MHz, CDCl3, 23°C) δ: 8.86-8.82 (m, 2H), 8.59 (s, 1H), 8.12 (dd, J = 8.0 Hz, 2.0 Hz, 1H), 8.06 (d, J = 8.0 Hz, 1H), 1.37 (s, 12H). Nuclear magnetic resonance carbon spectrum (13C NMR, 125 MHz, CDCl3, 23°C) δ: 145.53, 145.03, 144.37, 142.41, 137.31, 134.75, 131.90 (br), 128.44, 84.36, 24.86. high-resolution mass spectra (HRMS-FIA) m/z: [M + H]+ Calculated value 257.14558, measured value 257.14440.

References

[1] Organic Letters, 2009, vol. 11, # 13, p. 2860 - 2863
[2] Patent: WO2010/59943, 2010, A2. Location in patent: Page/Page column 86
[3] Journal of Medicinal Chemistry, 2011, vol. 54, # 13, p. 4735 - 4751
[4] Journal of the American Chemical Society, 2017, vol. 139, # 24, p. 8267 - 8276
[5] Organic Letters, 2018, vol. 20, # 6, p. 1530 - 1533