Sodium hydride → 2,7-Difluoro-3,6-bis[(2-methoxyethoxy)methoxy]-9h-xanthen-9-one

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Reaction Conditions

Reaction Steps

A cloudy solution of 8 (2.4 g, 9.1 mmol) in dry THF (50 mL) was treated with sodium hydride (1.1 g, 45.8 mmol) at 0° C. under an Ar atmosphere. The mixture was stirred at 0° C. for 30 min and then 2-methoxyethoxymethyl chloride (5.2 mL, 45.8 mmol) was added. The mixture was stirred at 0° C. for an additional 30 min and then warmed to room temperature overnight. The reaction mixture was cooled to 0° C., quenched with 1M citric acid (50 mL), and then 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 CH2Cl2/hexane/EtOAc=1:1:0.4 to yield 2.6 g (65%) of 9 as a white solid. Rf=0.47 (in CH2Cl2/hexane/EtOAc=1:1:0.4); 1H NMR (300 MHz, CDCl3) δ7.91 (d, 2H, J=10.6 Hz), 7.28 (d, 2H, J=6.5 Hz), 5.46 (s, 4H), 3.91 (m, 4H), 3.60 (m, 4H), 3.39 (s, 6H); 13C NMR (75 MHz, CDCl3) 6174.4, 153.3, 153.2, 151.4, 151.0, 150.9, 148.2, 115.2, 115.1, 111.8, 111.6, 104.8, 94.2, 71.3, 68.6, 59.0; 19F NMR (282 MHz, CDCl3) δ −137.0 (dd, 2 F); mass spectrum, calculated for C21H22F2O8 (MH+) 441.1, Found 441.0.

Provenance & Evidence