Benzoyl Peroxide → HCID 86720706, compound

Participants

Reaction Steps

A mixture of methyl 3-fluoro-5-methylbenzoate (1.0 g, 5.95 mmol), N-bromosuccinimide (1.27 g, 7.14 mmol), and dibenzoylperoxide (145 mg, 0.60 mmol) in CHCl3 (50 mL) was heated to reflux for 6 hours. After cooling to room temperature, the reaction mixture was quenched with saturated aqueous NaHCO3 (50 mL), and the layers were separated. The organic phase was washed with saturated aqueous NaHCO3 (50 mL) and then passed through a hydrophobic frit. The solvent was removed in vacuo and the residue was used directly in the next step without any further purification. To the residue was added 2-fluoroaniline (0.23 mL, 2.41 mmol) and potassium carbonate (454 mg, 3.29 mmL) in DMF (5.5 mL). The mixture was stirred at room temperature for 18 hours and then partitioned between EtOAc (30 mL) and water (20 mL). The layers were separated and the aqueous phase extracted with EtOAc (3×30 mL) The combined organic phases were washed with brine (20 mL) and dried over Na2SO4. The mixture was filtered and the solvent was removed in vacuo. The residue was purified on an SCX cartridge washing with MeOH and eluting with 3 to 10% NH3 in DCM. Further purification via silica gel chromatography, eluting with 0-20% EtOAc in isohexane, gave methyl 3-fluoro-5-(((2-fluorophenyl)amino)methyl)benzoate (CD6) as a yellow oil (133 mg, 8.1% over two steps).

Provenance & Evidence