Cesium carbonate → HCID 117746866, compound

Participants

Reaction Steps

A RBF was charged with (E)-ethyl 3-(2-amino-5-(benzylthio)phenyl)acrylate (4.729 g, 15.09 mmol, made via Method 42, Steps 1-2), 1-bromo-4-iodo-5-methoxy-2-methylbenzene (5.18 g, 15.84 mmol, Oakwood), Xantphos (0.437 g, 0.754 mmol), Pd2(dba)3 (0.345 g, 0.377 mmol), cesium carbonate (9.83 g, 30.2 mmol), and toluene (30 mL) were added. A reflux condenser was attached, and the mixture was heated to reflux. After 4 h, additional portions of Pd2(dba)3 (172 mg) and Xantphos (213 mg) were added. After 2 h, additional portions of cesium carbonate (ca. 2 g) and 1-bromo-4-iodo-5-methoxy-2-methylbenzene (600 mg) were added. Following an additional 30 min of reflux, mixture was cooled and filtered through celite. The filter pad was washed with EtOAc (3×). The filtrate was concentrated. The residue was concentrated from MeOH, and taken up in MeOH. The resulting suspension was heated to boiling, then sonicated and cooled to RT. The mixture was filtered, and the collected solid was washed with MeOH (3×) and dried under a stream of N2 (g) for 48 hrs to give (E)-ethyl 3-(5-(benzylthio)-2-((4-bromo-2-methoxy-5-methylphenyl)amino)phenyl)acrylate (5.21 g, 10.17 mmol, 67.4% yield) as a bright-yellow solid. 1H NMR (400 MHz, DMSO-d6) □=7.75 (d, J=15.9 Hz, 1 H), 7.66 (d, J=2.1 Hz, 1H), 7.42 (s, 1 H), 7.37-7.20 (m, 6 H), 7.14 (s, 1 H), 6.85 (d, J=8.5 Hz, 1 H), 6.62 (s, 1 H), 6.51 (d, J=15.9 Hz, 1 H), 4.23 (s, 2 H), 4.15 (q, J=7.0 Hz, 2 H), 3.78 (s, 3 H), 2.14 (s, 2 H), 1.23 (t, J=7.1 Hz, 3 H). m/z (ESI) 512.2 (M+H)+.

Provenance & Evidence