Potassium Carbonate → 5-(4-Chlorophenyl)-N-(2,2-diethoxyethyl)thiophene-2-carboxamide

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Reaction Steps

Add 5-chloro-thiophene-2-carboxylic acid (2,2-diethoxyethyl) amide (50.15 g, 0.18 mol), 4-chlorophenylboronic acid (29.84 g, 0.18 mol), potassium carbonate (50 g, 0.36 mol), [1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene)(3-chloropyridyl)]palladium (II) dichloride (4.40 g, 0.006 mol), and EtOH (1000 mL) to a 2 L three-necked round bottom flask equipped with a overhead stirrer, reflux condenser, nitrogen inlet/outlet, addition funnel, and thermocouple. Heat the resulting slurry for 35 min, then add activated carbon (5.8 g) and heat for an additional 30 min. Filter the resulting slurry through glass microfibre filter and rinse solids with EtOH (500 mL). Remove solvent from the filtrate under reduced pressure until 15-20% solvent remains. To this filtrate, add water (1300 mL) and stir the resulting slurry at room temperature for 1 h, then at 0-5° C. for 0.5 h. Filter the slurry, rinse the solids with water (1000 mL), and dry to afford 66 g of crude 5-(4-chlorophenyl)-thiophene-2-carboxylic acid (2,2-diethyoxyethyl) amide. Reflux the crude 5-(4-chlorophenyl)-thiophene-2-carboxylic acid (2,2-diethyoxyethyl) amide in heptane (1625 mL) for 1 h, then filter through a glass microfibre filter. Transfer the filtrate to a round bottom flask and remove solvent until 725 mL of solvent remained. Stir the mixture under chilled conditions for 40 minutes. Filter the resulting slurry, rinse with heptane (100 mL), and dry to afford 41 g (64%) as a white solid. 1H NMR (500 MHz, CDCl3): δ 1.25 (t, J=7.0 Hz, 6H), 3.57-3.62 (m, 4H), 3.73-3.79 (m, 2H), 4.62 (t, J=5.5 Hz, 1H), 6.20 (bs, 1H), 7.24 (d, J=4.5 Hz, 1H), 7.38 (d, J=9.0 Hz, 2H), 7.45 (d, J=4.5 Hz, 1H), 7.54 (d, J=9.0 Hz, 2H).

Provenance & Evidence