Dichloromethane → HCID 86716065, compound

Participants

Reaction Steps

A mixture of 4-bromo-3-fluoroaniline (6.54 g, 34.4 mmol), 2-phenylmalonic acid (7.44 g, 41.3 mmol), and POCl3 (32.0 mL, 344 mmol) was stirred at reflux (130° C. aluminum block temperature) for 3 hours. The dark solution was then allowed to cool to room temperature and diluted with DCM (70 mL). This was treated with 100 mL ice and stirred on an ice bath for ˜5 min, and was then treated with 15 M NH4OH dropwise (6 mL) and removed from the ice bath. Stirring at room temperature caused the reaction to warm to a gentle reflux (42° C.), and the reaction was chilled on an ice bath intermittently. After ˜10 min stirring at room temperature the exotherm moderated, the aqueous layer was extracted with DCM (30 mL), and the combined dark clear organic layers were concentrated to provide a brown solid. This was dry load flash chromatographed with a 20% DCM/heptane to 100% DCM gradient to afford a ˜2:1 mol ratio of the title compound and the 5-fluoro regioisomer as a light yellow solid. A portion of this was dry load flash chromatographed with a 20% toluene/heptane to 100% toluene gradient to provide the title compound eluting at 60-70% toluene/heptane.

Provenance & Evidence