Isatin → 7-(Thiophen-3-yl)indoline-2,3-dione

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Reaction Steps

This compound was prepared according to the procedure described by Lisowski et al. J. Org. Chem., 2000, 65, 4193. To a 1 L 3-necked round-bottomed flask fitted with a reflux condenser were added intermediate 6 (2.0 g, 7.3 mmol) and tetrakis[triphenylphosphine]palladium (0.424 g, 0.367 mmol), followed by 115 mL ethylene glycol dimethyl ether. The atmosphere in the reaction vessel was made inert by opening to vacuum, then to a positive pressure of nitrogen (3×). Next, 3-thiopheneboronic acid (Aldrich, 1.03 g, 8.06 mmol) and a solution of sodium bicarbonate (1.23 g, 14.7 mmol) in 115 mL water were added, and the evacuation/nitrogen procedure repeated one more time. The reaction mixture was then refluxed until t.l.c. (10% ethyl acetate in dichloromethane) showed complete disappearance of 7-iodoisatin, 6, (1-3 hours). After cooling to room temperature, the organic solvent was removed under reduced pressure. The residue was diluted with 1M aqueous hydrochloric acid and extracted into ethyl acetate (3×). The organic layer was washed with brine, dried over anhydrous magnesium sulfate, filtered, and evaporated under reduced pressure. The crude product was purified by flash chromatography over silica gel, eluting with 3% ethyl acetate in dichloromethane, to give 7-(thien-3-yl)isatin, Intermediate 8, as a bright red crystalline material (0.91 g, 54% yield): 1H NMR (400 MHz, DMSO-D6) δ 7.15 (t, 1H) 7.36 (dd, J=4.9, 1.4 Hz, 1H) 7.50 (dt, J=7.3, 1.0 Hz, 1H) 7.68 (d, J=1.5 Hz, 1H) 7.71 (m, 2H) 7.75 (dd, J=2.9, 1.4 Hz, 1H) 10.86 (s, 1H).

Provenance & Evidence