Synthesis of Biarylic Aldehyde Derivative

5-Chloro-2-hydroxy-4-((2-methyl-[1,1′-biphenyl]-3-yl)methoxy)benzaldehyde
(2b) (1.00 mg, 2.96 μmol, 1.0 equiv) was mixed
with cesium carbonate (Cs₂CO₃, trace-metal basis)
(1.93 mg, 5.92 μmol, 2.0 equiv) (Merck KGaA, Darmstadt, Germany)
under N₂ atmosphere in a round-bottom flask. 3-(Bromomethyl)benzonitrile
(1.16 mg, 5.92 μmol, 2.0 equiv) (Merck KGaA, Darmstadt, Germany)
and catalytic amounts of potassium iodide (KI) (0.04 mg, 0.24 μmol,
0.1 equiv) (Merck KGaA, Darmstadt, Germany) were dissolved in 0.5
mL of dry DMF, added to the flask, and continuously stirred at room
temperature for 1 day. The reaction mixture was mixed with EtOAc,
washed with Milli-Q H₂O, and dried over Na₂SO₄. The product was purified by silica gel chromatography using
a 1:1 hexane/EtOAc mixture. The organic solvents were removed in vacuo yielding a colorless solid (1.07 mg, 76% yield).
Purity: 96.49% as determined by HPLC setup 1, UV detector: 254
nm.
¹H NMR (600 MHz, CDCl₃): δ 10.32
(s,
1H), 7.92 (s, 1H), 7.73 (s, 1H), 7.69–7.67 (m, 2H), 7.55 (t, J = 7.8 Hz, 1H), 7.45–7.31 (m, 3H), 7.38–7.36
(m, 1H), 7.32–7.28 (m, 4H), 6.62 (s, 1H), 5.21 (s, 2H), 5.20
(s, 2H), 2.27 (s, 3H).
¹³C NMR (151 MHz, CDCl₃): δ 186.80,
160.68, 160.08, 143.40, 141.67, 137.28, 134.31, 133.69, 132.37, 131.55,
130.77, 130.73, 130.46, 129.97, 129.50, 128.34, 127.71, 127.22, 125.91,
119.54, 118.40, 117.23, 113.35, 98.79, 70.69, 70.00, 16.47.
ESI-MS ([M + Cl]⁻): m/z calculated ([C₂₉H₂₂ClNO₃ + Cl]⁻) = 502.0982 Found = 502.1029.