Ethanol → Ethyl 6-methoxybenzofuran-3-carboxylate

Temperature

80 °C

In a steel high-pressure reaction vessel, a solution of trifluoro-methanesulfonic acid 6-methoxy-benzofuran-3-yl ester (9.10 g, 30.7 mmol) in dimethylformamide (120 mL) is bubbled with carbon monoxide gas for 10 minutes. Ethanol (60 mL), triethylamine (9.25 mL), Pd(OAc)2 (0.20 g), bis-(1,3-diphenylphosphino)propane (0.38 g) are added to the reaction mixture. The mixture vessel is sealed, charged with carbon monoxide (10 g, 30 psi), and heated to 80° C. for 4.5 hours. The mixture is concentrated under reduced pressure and diluted with water (300 mL), and extracted with EtOAc (150 mL×2). The combined organic layers are dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude product is purified via flash chromatography eluting with 15% EtOAc/Hexanes. The appropriate fractions are combined and concentrated under reduced pressure to afford the title compound (5.50 g, 81%). 1H NMR (400 MHz, CDCl3): δ 8.16 (s, 1H), 7.88 (d, 1H), 7.01 (s, 1H), 6.96 (d, 1H), 4.38 (q, 2H), 3.81 (s, 3H), 1.40 (t, 3H).

1. customThe mixture vessel is sealed
2. concentrationThe mixture is concentrated under reduced pressure
3. additiondiluted with water (300 mL)
4. extractionextracted with EtOAc (150 mL×2)
5. dry with materialThe combined organic layers are dried over Na2SO4
6. filtrationfiltered
7. concentrationconcentrated under reduced pressure
8. customThe crude product is purified via flash chromatography
9. washeluting with 15% EtOAc/Hexanes
10. concentrationconcentrated under reduced pressure

ORD record

ord-62a0d1a7880b48e18eb38ac64989ba31

Source dataset

uspto-grants-2011_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07863302B2