Sodium Carbonate → 6-(4-(1-Hydroxyethyl)pyridin-3-yl)-2-naphthonitrile

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Reaction Conditions

Reaction Steps

A mixture of 6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-naphthonitrile 2c (233 mg, 0.835 mmol), 1-(3-bromopyridin-4-yl)ethanol (153 mg, 0.759 mmol, prepared according to the procedure described in Heterocyles 1993, 35, 151-169), sodium carbonate (2M in water, 0.759 mL, 1.518 mmol), bis(triphenylphosphine)palladium(II) chloride (26.6 mg, 0.038 mmol) in DMF (3.035 mL) was heated to 100° C. for 1 hr. The mixture was quenched with saturated NaHCO3 solution and extracted with EtOAc twice. The combined extracts were dried over anhydrous magnesium sulfate, filtered, and concentrated. The residue was purified twice via Biotage (20-100% EtOAc/heptane; 25M column). 47 mg of racemic title compound was isolated as white solid, and was subsequently separated by chiral HPLC (ChiralPak AS-H column, 2.1×250 mm, 16 mL/min, 70% heptane 30% ethanol) to 2-(enantiomer-1) (13 mg, 6%) (retention time: 11.74 min) and 2-(enantiomer-2) (12 mg, 6%) (retention time: 19.90 min). 1H NMR (400 MHz, CDCl3) δ ppm 1.34 (d, J=6.3 Hz, 3H), 5.28 (q, J=6.5 Hz, 1H), 7.59 (d, J=8.3 Hz, 1H), 7.75 (d, J=7.9 Hz, 1H), 7.91 (s, 1H), 8.39 (d, J=5.0 Hz, 1H), 8.55 (s, 1H), 8.70 (d, J=6.2 Hz, 1H). LC-MS (M+1) 275.1, t=1.06 min.

Provenance & Evidence