反应详情

To a solution of 3.5-difluoroanisole (25 g; 175 mmol) in dichloromethane (150 ml) cooled at 0° C. was added titanium tetrachloride (30.7 ml; 280 mmol). To this mixture was added dropwise over 10 minutes dichloromethyl methylether (15.8 ml; 175 mmol), and after complete addition the mixture was stirred at room temperature for 1 hour. The reaction was poured onto ice/water (500 ml) and extracted with DCM (3×300 ml). The combined DCM layers were washed with water (500 ml), saturated NaCl (200 ml), dried over Na2SO4, filtered and evaporated. The residue was purified by column chromatography on silica-eluting with a gradient rising from 15% Et2O in isohexanes rising to 30% Et2O in isohexanes to give the title compound (11.2 g, 37%) as a white solid.

1. additionafter complete addition the mixture
2. additionThe reaction was poured onto ice/water (500 ml)
3. extractionextracted with DCM (3×300 ml)
4. washThe combined DCM layers were washed with water (500 ml), saturated NaCl (200 ml)
5. dry with materialdried over Na2SO4
6. filtrationfiltered
7. customevaporated
8. customThe residue was purified by column chromatography on silica-
9. washeluting with a gradient