1-[6-(4-Methylphenyl)pyridin-3-yl]ethanone synthesis

Yield:1216790-93-0 92%

Reaction Conditions:

with bis-triphenylphosphine-palladium(II) chloride;sodium carbonate in water;acetonitrile at 80; for 14 h;Suzuki Coupling;

Steps:

7 Example 7: 1-(6-p-tolyl-pyridin-3-yl)-ethanone

According to the general Suzuki coupling of pyridine compounds, 5-acetyl-2-bromopyridine 38 (0.394 g, 1.97 mmol), 4-tolylboronic acid (0.535 g, 3.94 mmol), Na₂CO₃ (0.146 g, 1.38 mmol), Pd(PPh₃)₂Cl₂ (0.042 g, 0.06 mmol, 3% Pd), acetonitrile (7.8 mL), water (7.8 mL) were heated at 80° C. for 14 h (overnight). Following the general workup and flash chromatography (SiO₂, 20 g, 5% EtOAc/hexanes) coupled ketone was obtained as a white solid 41 (0.381 g, 92%); TLC R_f=0.4 (25% EtOAc/hexanes); mp 106-107.5° C.; ¹H NMR (500 MHz, CDCl₃) δ 9.19 (d, J=2.2 Hz, 1H), 8.24 (dd, J=8.3, 2.3 Hz, 1H), 7.95 (d, J=8.2 Hz, 2H), 7.79 (d, J=8.4 Hz, 1H), 7.29 (d, J=8.4 Hz, 2H), 2.63 (s, 3H), 2.40 (s, 3H); ¹³C NMR (125 MHz, CDCl₃) δ 196.6, 161.0, 150.2, 140.5, 136.4, 135.5, 130.5, 129.8, 127.4, 26.8, 21.5; IR (neat cm^-1) 3024, 2911, 2853, 2042, 1671, 1589, 1555, 1371, 1279, 1141, 819, 762; HRMS (DART, M₊+H) m/z 212.1093 (calculated for C₁₄H₁₄NO, 212.1075).

References:

US2015/225353,2015,A1 Location in patent:Paragraph 0092