2,4-Difluorobenzylamine → HCID 66882984, compound

Participants

Reaction Steps

Alternatively, 8-chloro-3-(4-phenoxyphenyl)isochromen-1-one (48 mg, 0.14 mmol) and 2,4-difluorobenzylamine (24 μL, 0.20 mmol) were combined in toluene (2.0 mL) in a round-bottomed flask under nitrogen. To the resulting mixture was added a solution of methyl aluminoxane (0.11 mL, of a 1.5 M solution in toluene, 0.16 mmol). The resulting yellow solution was then heated to reflux. TLC of the reaction mixture after 1 hour at reflux showed no 8-chloro-3-(4-phenoxyphenyl)isochromen-1-one remaining. Heating was discontinued and the reaction was allowed to cool to ambient temperature. The reaction was then quenched by the addition of 1N HCl (aq.) (5 mL), and diluted with EtOAc (25 mL). The layers were separated and the acidic aqueous layer was extracted with EtOAc (3×10 mL). The combined organic layers were washed with H2O (10 mL), saturated aqueous NaHCO3 (10 mL), then brine. The organic layer was dried over Na2SO4, filtered, and concentrated under reduced pressure to afford a white solid. The crude solid was purified by silica gel column chromatography by adsorbing the material onto silica gel from a CH2Cl2 solution, loading the resulting solid onto the column and eluting with a gradient from 0% to 20% EtOAc/hexane. The main peak that eluted was collected to afford a compound of formula (W), 2-chloro-N-(2,4-difluorobenzyl)-6-[2-oxo-2-(4-phenoxyphenyl)ethyl]benzamide, (54 mg, 79% yield) as a white solid; 1H-NMR (400 MHz, CDCl3): δ 7.87-7.82 (2H, m), 7.46-7.41 (2H, m), 7.35-7.21 (4H, m), 7.14-7.10 (2H, m), 7.05-7.02 (1H, m), 7.01-6.96 (2H, m), 6.66-6.60 (1H, m), 6.53-6.47 (1H, m), 6.43 (1H, t, J=6.1 Hz), 4.49 (2H, d, J=6.1 Hz), 4.25 (2H, s); which could be used in the next step to produce a corresponding compound of formula (Id).

Provenance & Evidence