Dimethylformamide → 4-(2-Formyl-4-(4-methoxyphenyl)thiophen-3-yl)-3-methylbenzonitrile

Participants

Reaction Steps

A solution of freshly prepared LDA (0.8 mL, 1.64 mmol) in anhydrous tetrahydrofuran (7 mL) was added slowly a solution of 4-(4-(4-methoxyphenyl)thiophen-3-yl)-3-methylbenzonitrile (Scheme I, 3, X1=4-methoxyphenyl, X2=4-cyano-2-methylphenyl) (500 mg, 1.637 mmol) in anhydrous tetrahydrofuran (6 mL) under nitrogen at −78° C. After being stirred for 15 min., a solution of dimethylformamide (0.14 mL, 1.804 mmol) in anhydrous tetrahydrofuran (3 mL) was dropwise added. The resulting mixture was stirred for 1 h at −78° C., and at room temperature for 3 h. The reaction was quenched with water (50 mL), and extracted with ethyl acetate (40 mL×3). The combined organic extracts were washed with water (30 mL), brine (50 mL), dried over anhydrous sodium sulfate, evaporated, and purified by column chromatography (silica gel, petroleum ether/ethyl acetate=20:1) to afford 4-(2-formyl-4-(4-methoxyphenyl)thiophen-3-yl)-3-methylbenzonitrile (Scheme I, 4A, X1=4-methoxyphenyl, X2=4-cyano-2-methylphenyl) (0.16 g, yield 29.3%) as a white solid (confirmed by NOE). 1H NMR (DMSO-d6 400 MHz): δ 9.46 (s, 1H), 8.31 (d, J=1.2 Hz, 1H), 7.83 (s, 2H), 7.67 (d, J=8.8 Hz, 1H), 7.07 (d, J=8.8 Hz, 2H), 6.89 (d, J=8.8 Hz, 2H), 3.77 (s, 3H), 1.94 (s, 3H).

Provenance & Evidence