Acetic Acid → (Z)-methyl 2-(5-bromothiophene-2-carbonyl)-3-(4-chlorophenyl)acrylate

Participants

Reaction Conditions

Reaction Steps

To a 500 mL round bottom flask was added a solution of methyl 3-(5-bromo-2-thienyl)-3-oxopropanoate (4.402 g, 16.73 mmol), 4-chlorobenzaldehyde (2.822 g, 20.08 mmol) and piperidine (0.165 mL, 1.673 mmol) in anhydrous benzene (200.0 mL, 2238 mmol). Acetic acid (0.665 mL, 11.712 mmol) was added and the reaction mixture was fitted with a Dean-Stark trap and the bath was heated to 92° C. and allowed to reflux for 18 hours. The reaction was cooled to ambient temperature and concentrated under reduced pressure. The crude material was split in half and dry loaded onto silica gel and then purified using a ISCO (40 g cartridge, gradient hexanes to 40% EtOAc over 30 min) to afford the title compound (6.26 g, 92%) as a yellow solid. LC/MS (AA) ES− 385, 387, 389(dmso-d6, 400 MHz): δ 7.89 (s, 1H), 7.34-7.24 (m, 5H), 7.00 (d, 1H), 3.71 (s, 3H).

Provenance & Evidence