反应详情

To a solution of ethyl 2-(6-chloropyridazin-3-yl)-2-fluoroacetate (36.6 g, 167 mmol) in anhydrous THF (500 mL) was added lithium hexamethyldisilazide (201 ml, 201 mmol) drop-wise at −78° C. After 15 minutes, a solution of Selectfluor (71.2 g, 201 mmol) in DMF (183 mL) was added drop-wise. Upon complete addition, the reaction was allowed to warm to ambient temperature over a 30 min period. Saturated NH4Cl (70 mL) was then added, and THF was removed via rotary evaporation. The resulting residue was diluted with water (500 mL), extracted with Et2O (3×100 mL), dried with MgSO4, filtered, and concentrated to dryness. The resulting material was purified via MPLC (Hex:EtOAc, 8:2) to provide ethyl 2-(6-chloropyridazin-3-yl)-2,2-difluoroacetate 45D (20.8 g, 88 mmol, 52.5%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.25 (t, J=7.07 Hz, 3 H) 4.38 (q, J=7.07 Hz, 2 H) 8.26 (d, J=9.09 Hz, 1 H) 8.33 (d, J=8.84 Hz, 1 H). ESI-MS:m/z 237.1 (M+H)+.

1. additionUpon complete addition
2. customTHF was removed via rotary evaporation
3. additionThe resulting residue was diluted with water (500 mL)
4. extractionextracted with Et2O (3×100 mL)
5. dry with materialdried with MgSO4
6. filtrationfiltered
7. concentrationconcentrated to dryness
8. customThe resulting material was purified via MPLC (Hex:EtOAc, 8:2)