Dimethylformamide → 4-Ethoxy-6-formyl-quinoline-3-carbonitrile

A mixture of 4-ethoxy-6-iodo-quinoline-3-carbonitrile (example 14d, 6.4 g, 20 mmol), trethylamine (6.9 mL, 50 mmol), diphenylpropylphosphine (dpp, 0.23 uL, 1 mmol) and palladium(II) acetate (0.22 g, 1 mmol) in dry N,N-dimethylformamide (120 mL) in pressure tube was stirred under carbon monoxide at 75 psi at room temperature for 10 min. After addition of trihexylsilane (14 mL, 40 mmol), the mixture was then stirred under carbon monoxide at 75 psi at 80° C. for 3 h. The reaction was allowed to cool to 25° C. and then extracted with ethyl acetate (2×200 mL). The combined organic layers were successively washed with a saturated aqueous sodium bicarbonate solution (3×50 mL) and water (3×50 mL), dried over sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 70-230 mesh, 5%-40% ethyl acetate in hexanes in 30 min) afforded 4-ethoxy-6-formyl-quinoline-3-carbonitrile (2.3 g, 51%) as a white solid. LC-MS m/e 227 (MH+).

1. stirringthe mixture was then stirred under carbon monoxide at 75 psi at 80° C. for 3 h
2. temperatureto cool to 25° C.
3. extractionextracted with ethyl acetate (2×200 mL)
4. washThe combined organic layers were successively washed with a saturated aqueous sodium bicarbonate solution (3×50 mL) and water (3×50 mL)
5. dry with materialdried over sodium sulfate
6. filtrationfiltered
7. concentrationconcentrated in vacuo

ORD record

ord-bb594acf1ddd4214a441d87241a63da2

Source dataset

uspto-grants-2007_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07250515B2