Pyridine → HCID 53712331, compound

Participants

Reaction Steps

A mixture of cyanoacetic acid (7.56 g, 88.9 mmol), thiophene-3-carbaldehyde 79 (Aldrich, Wis.) (10.97 g, 97.8 mmol), ammonium acetate (0.36 g, 4.7 mmol), toluene (89 mL), and pyridine (47 mL) was heated at reflux for 20 h in a flask fitted with a Dean-Stark trap and condenser. After evaporation of solvents, a solution of the residue in CH2Cl2 (300 mL) was washed with water, dried over Na2SO4, filtered, and evaporated. The crude product was isolated by flash chromatography on a silica gel column using 10% to 20% gradient of EtOAc in hexane as eluent to afford 3-thiophen-3-yl acrylonitrile (6.38 g) in a 1.8 to 1 ratio of trans to cis isomer as a dark brown oil. The product was then dissolved in pyridine (100 mL) and EtOH (20 mL). To the resulting solution was added NaBH4 (3.57 g, 94.4 mmol). The solution was then heated at 100° C. until completion of the reaction approx. (4 h) and concentrated in vacuo. The crude product was purified by silica gel column chromatography (eluent: 11% EtOAc in hexane). The major fractions were combined and concentrated to give 80 (4.03 g) as a yellow liquid. 1H NMR (400 MHz, d6-DMSO) δ: 7.50 (dd, J=3.0 and 5.0 Hz, 1H), 7.31 (m, 1H), 7.07 (dd, J=1.0 and 5.0 Hz, 1H), 2.89 (m, 2H), 2.81 (m, 2H). MS (EI) m/z (M+H+) 138.

Provenance & Evidence