Oxalyl chloride → Methanone, bis(5-fluoro-2,4-dihydroxyphenyl)-

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Reaction Steps

2,4-dimethoxy-5-fluorobenzoic acid 6 (5.4 g, 27 mmol) in dry CH2Cl2 (100 mL) was treated with 10.6 mL of oxalyl chloride under an Ar atmosphere and stirred at room temperature overnight. The excess reagent and solvent were removed under reduced pressure. The residue, 2,4-dimethoxy-5-fluorobenzoyl chloride, was redissolved in anhydrous CH2Cl2 (125 mL). 1,3-dimethoxy-4-fluorobenzene 3 (3.29 mL, 26 mmol) and AlCl3 (10.8 g, 81 mmol) were added at 0° C. After stirring at 0° C. for 1 h, the reaction mixture was allowed to warm to room temperature for 67 h, the mixture was then hydrolyzed with 1M HCl (300 mL) at 0° C. and extracted with EtOAc. The combined organic layers were washed with brine, dried over Na2SO4 and concentrated in vacuo. The crude product was purified by flash column chromatography, eluting with 30%-40% EtOAc in hexane to yield 7 (3.3 g, 44%) as a yellow solid. 1H NMR (300 MHz, MeOH-d4) 7.14 (d, 2H, J=11.5 Hz), 6.46 (d, 2H, J=7.4 Hz); 13C NMR (75 MHz, MeOH-d4) δ 199.1, 159.0, 152.9, 152.7, 147.7, 144.5, 119.2, 118.9, 114.2, 114.1, 106.1, 106.0; 19F NMR (282 MHz, MeOH-d4). δ −149.8 (dd, 2F).

Provenance & Evidence