3-Bromo-4,5-dimethoxybenzaldehyde → 3,4-Dimethoxy-5-thien-2-yl-benzaldehyde

Ex-1D: A solution of 5-bromo-3,4-dimethoxybenzaldehyde (10.23 g, 41.7 mmol) in 359 mL of ethylene glycol dimethyl ether was purged with nitrogen gas for 30 min. The solution was treated with tetrakis(triphenylphosphine)palladium(0) (5.0 g, 4.3 mmol), thiophene-2-boronic acid (8.01 g, 62.6 mmol), and a solution of 2 N sodium carbonate 72 mL, 3.45 mmol). The reaction was refluxed for 16 h. The reaction mixture was concentrated, diluted with an aqueous solution of saturated sodium bicarbonate (75 mL), and extracted with dichloromethane (2×100 mL). The organic layer was dried over sodium sulfate and concentrated to a brown solid. The crude material was purified by silica gel chromatography (1:1 ethyl acetate/hexanes) to give 9.42 g (90%) of the desired 3,4-dimethoxy-5-(thien-2-yl)benzaldehyde product. 1H-NMR (300 MHz, CDCl3) δ 9.94 (s, 1H), 7.79 (d, 1H), 7.57 (dd, 1H), 7.41 (d, 1H), 7.36 (d, 1H), 7.13 (dd, 1H), 3.97 (s, 3H), 3.93 (s, 3H).

1. temperatureThe reaction was refluxed for 16 h
2. concentrationThe reaction mixture was concentrated
3. additiondiluted with an aqueous solution of saturated sodium bicarbonate (75 mL)
4. extractionextracted with dichloromethane (2×100 mL)
5. dry with materialThe organic layer was dried over sodium sulfate
6. concentrationconcentrated to a brown solid
7. customThe crude material was purified by silica gel chromatography (1:1 ethyl acetate/hexanes)

ORD record

ord-ffe68f0513c241bd8c2d2a4b859c46bf

Source dataset

uspto-grants-2006_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07094801B2