反应详情

To a solution of 2,4-difluoro-1-iodo-benzene (12.0 g) in anhydrous THF (200 mL) was added a solution of isopropylmagnesium chloride lithium chloride complex (52.9 mL, 14% solution in THF) slowly over 10 min at room temperature. After stirring for 1 h, a solution of 3-(4-bromo-phenyl)-2-cyano-acrylic acid ethyl ester (10.0 g; example 74, step 1) in anhydrous THF (100 mL) was added and stirring continued at room temperature. After 1 h, a saturated aq. solution of ammonium chloride was added (100 mL), the phases separated and the aqueous layer extracted with ethyl acetate (3×100 mL). The combined organic phases were dried over sodium sulfate and the crude reaction product purified by silica gel chromatography using a MPLC system (CombiFlash Companion, Isco Inc.) eluting with a gradient of n-heptane/ethyl acetate (1:0 to 3:1) to provide the title compound as a light yellow oil. MS (ESI−): m/z=391.9 ([M−H]−).

1. stirringstirring
2. customcontinued at room temperature
3. waitAfter 1 h
4. customthe phases separated
5. extractionthe aqueous layer extracted with ethyl acetate (3×100 mL)
6. dry with materialThe combined organic phases were dried over sodium sulfate
7. customthe crude reaction product
8. custompurified by silica gel chromatography
9. washeluting with a gradient of n-heptane/ethyl acetate (1:0 to 3:1)