Pivalic acid → (E)-methyl 3-(4-((2-(2-isopropylphenyl)-6-methoxybenzo[b]thiophen-3-yl)oxy)phenyl)acrylate

Participants

Reaction Conditions

Reaction Steps

To a solution of (E)-4-(4-((6-methoxybenzo[b]thiophen-3-yl)oxy)phenyl)but-3-en-2-one (45 g, 132 mmol) in anhydrous DMA (450 mL) at room temperature was added 1-iodo-2-isopropylbenzene (57 g, 231.6 mmol), chloro[2-(dicyclohexylphosphino)-3,6-dimethoxy-2′,4′,6′-tri-i-propyl-1,1′-biphenyl][2-(2-aminoethyl)phenyl]palladium(II) (BrettPhos Palladacycle 1st generation, 6.34 g, 7.93 mmol), trimethylacetic acid (40.5 g, 397 mmol) and potassium carbonate (55 g, 397 mmol). The resulting mixture was heated at 140° C. for 1.5 hours. The reaction mixture was cooled down to 50° C. The reaction was diluted with EtOAc (400 mL) and let to cool down to room temperature. As the reaction cooled, a precipitate formed and was removed by filtration. The mother liquor was washed with water and brine, dried over anhydrous Na2SO4, filtered and concentrated in vacuo to give the crude product, which was purified by column chromatography (SiO2, 10-20% EtOAc/heptane) to afford (E)-methyl 3-(4-((2-(2-isopropylphenyl)-6-methoxybenzo[b]thiophen-3-yl)oxy)phenyl)acrylate (47 g, 102.5 mmol). 1H NMR (400 MHz, CDCl3) δ ppm=7.61 (d, J=15.9 Hz, 1H), 7.42-7.29 (m, 7H), 7.15 (ddd, J=8.1, 5.7, 2.8 Hz, 1H), 6.97 (dd, J=8.8, 2.3 Hz, 1H), 6.91-6.85 (m, 2H), 6.29 (d, J=16.0 Hz, 1H), 3.91 (s, 3H), 3.80 (s, 3H), 3.26 (p, J=6.8 Hz, 1H), 1.19 (d, J=6.9 Hz, 6H), LC/MS (m/z, MH+): 459.5.

Provenance & Evidence