2-Methoxy-5-(4,4,5,5-tetraMethyl-1,3,2-dioxaborolan-2-yl)aniline

Synthesis

General procedure: 5-bromo-2-methoxyaniline (3.22 g, 15.93 mmol) and pinacol ester of bis(diphenylphosphine)ferrocene dichloropalladium(II) (0.34 g, 0.48 mmol) were added to a reaction flask under nitrogen protection with potassium acetate (8.9 g, 90.83 mmol), bis(diphenylphosphine)ferrocene dichloropalladium(II) (0.34 g, 0.48 mmol) and anhydrous DMSO (40 mL). The reaction mixture was stirred at 80 °C for 8 hours. After completion of the reaction, the reaction was quenched with saturated aqueous NaCl (30 mL) and extracted with ether (3 x 20 mL). The organic phases were combined, dried with magnesium sulfate, filtered and concentrated. The crude product was purified by fast column chromatography (stationary phase: silica gel 230-400 mesh, mobile phase: 9:1 hexane/ethyl acetate). All homogeneous fractions of the grades were collected and concentrated to afford the target product 2-methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (3.18 g, 80% yield) as a brown slurry. νmax (DCM)/cm1: 2926.38, 1599.02, 1431.11, 1356.01, 1221.39, 1142.48. 1H NMR (CDCl, 400MHz) δH ppm: 1.35 (12H, s, 2*C(CH)) ), 3.89 (3H, s, OCH), 6.15 (2H, br, NH), 7.18 (1H, d, J=8.0Hz, ArH), 7.25 (1H, d, J=2.5Hz, ArH), 7.29 (1H, s, ArH).13C NMR δC ppm: 24.5 (4*CH), 55.1 (OCH) 83.2 (2*C(CH)) , 105.5 (ArCH), 113.7 (ArC), 120.6 (ArCH), 125.8 (ArCH), 135.0 (ArC), 149.7 (ArC).

References

[1] Patent: US2015/18566, 2015, A1. Location in patent: Paragraph 0685; 0686; 0687; 0688; 0689
[2] Journal of Medicinal Chemistry, 2015, vol. 58, # 9, p. 3767 - 3793
[3] Patent: US2016/318895, 2016, A1. Location in patent: Paragraph 0303