Potassium Carbonate → 2-(2,4-Dichloro-benzoyl)-6-m-tolyl-benzofuran-3-carboxylic acid ethyl ester

Temperatur

80 °C

To a solution of 2-(2,4-Dichloro-benzoyl)-6-trifluoromethanesulfonyloxy-benzofuran-3-carboxylic acid ethyl ester from step 4 (162 mg, 0.32 mmol, 1 eq) in anhydrous N,N-dimethylformamide (2 mL) were sequential added 3-methyl benzene boronic acid (64.6 mg, 0.63 mmol, 1.5 eq), potassium carbonate (87.6 mg, 0.63 mmol, 2 eq) and tetrakis(triphenylphosphine)palladium(0) (73.2 mg, 0.06 mmol, 0.2 eq) under argon. The reaction mixture was degassed for 5 min. The reaction was then stirred at 80° C. for 4 h followed by stirred at rt for 12 h. The mixture was cooled to room temperature then poured into ethyl acetate (10 mL) and water (10 mL). The aqueous layer was extracted with ethyl acetate (2×10 mL). Combined the organic layer was washed by water (2×10 mL), dried over Na2SO4, filtrated, and evaporated in vacuo. The residue was purified by pre-HPLC to afford an yellow solid (91.3 mg, 63%) as product. 1H-NMR (CDCl3): δ 8.04 (d, J=8.3 Hz, 1H), 7.73 (s, 1H), 7.64 (dd, J=1.5, 8.3 Hz, 1H), 7.57 (d, J=8.3 Hz, 1H), 7.47 (d, J=1.9 Hz, 1H), 7.41(m, 2H), 7.36(dd, J=1.9, 8.3 Hz, 1H), 7.34 (t, 1H), 7.19 (d, J=8.3 Hz, 1H), 4.245 (q, 2H), 2.43 (s, 3H), 1.28 (t, 3H); LC-MS (MH+=453/455).

1. customThe reaction mixture was degassed for 5 min
2. stirringby stirred at rt for 12 h
3. temperatureThe mixture was cooled to room temperature
4. additionthen poured into ethyl acetate (10 mL) and water (10 mL)
5. extractionThe aqueous layer was extracted with ethyl acetate (2×10 mL)
6. washwas washed by water (2×10 mL)
7. dry with materialdried over Na2SO4
8. filtrationfiltrated
9. customevaporated in vacuo
10. customThe residue was purified by pre-HPLC

ORD-Eintrag

ord-d96e21afab8f40c7ac095834a94d9d97

Quelldatensatz

uspto-grants-2008_09

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07420066B2