Cesium carbonate → (E)-ethyl 3-(5-(benzylthio)-2-((4-bromo-2-methoxyphenyl)amino)phenyl)acrylate

Participants

Reaction Conditions

Reaction Steps

A RBF was charged with (E)-ethyl 3-(2-amino-5-(benzylthio)phenyl)acrylate (2.39 g, 7.63 mmol, made via Method 42, Steps 1-2), 4-bromo-1-iodo-2-methoxybenzene (2.86 g, 9.15 mmol), Xantphos (0.221 g, 0.381 mmol), Pd2(dba)3 (0.175 g, 0.191 mmol), and cesium carbonate (4.97 g, 15.25 mmol) were added. A reflux condenser was attached and the flask was lowered into a 110° C. heating bath. After 2 h, an additional portion of cesium carbonate (1.4 g) was added, and the bath temperature was raised to 120° C. The mixture was heated for another 2 h then cooled to room temperature, diluted with EtOAc, and filtered through celite with the aid of EtOAc. The filtrate was concentrated. The oily residue was taken up in 2-PrOH. The mixture was concentrated to give a yellow solid with some oily solid present. The mixture was taken up in 2-PrOH to give a suspension, and the suspension was stirred for 16 hrs. The mixture was filtered, and the filtered solid was washed with 2-PrOH (3×). The collected solid was dried on the filter under a flow of N2 (g) for 15 min to give (E)-ethyl 3-(5-(benzylthio)-2-((4-bromo-2-methoxyphenyl)amino)phenyl)acrylate (3.136 g, 6.29 mmol, 83% yield) as a bright-yellow solid. 1 H NMR (400 MHz, DMSO-d6) □=7.72 (d, J=16.0 Hz, 1H), 7.68 (d, J=2.2 Hz, 1 H), 7.47 (s, 1 H), 7.37-7.19 (m, 6 H), 7.13 (d, J=2.2 Hz, 1 H), 6.94 (dd, J=2.2, 8.4 Hz, 1 H), 6.86 (d, J=8.5 Hz, 1 H), 6.55 (s, 1 H), 6.52 (d, J=7.7 Hz, 1H), 4.24 (s, 2 H), 4.15 (q, J=7.1 Hz, 2 H), 3.82 (s, 3 H), 1.23 (t, J=7.1 Hz, 3 H). m/z (ESI) 498.0 (M+H)+.

Provenance & Evidence