反应详情

To a mixed solution of 4-(benzyloxy)-1-bromo-2-fluorobenzene (187 g, 665 mmol) described in Production Example 1-2-4 and 1,4-dioxane (300 mL) were added copper iodide (I) (12.6 g, 66.1 mmol), sodium iodide (200 g, 1.33 mol) and N,N′-dimethylethylenediamine (14.0 mL, 132 mmol) at room temperature, and the resultant mixture was stirred under a nitrogen atmosphere at 110 to 115° C. for 19 hours. The reaction mixture was cooled to room temperature, then water and ethyl acetate were added to the reaction mixture, the resultant mixture was filtrated using Celite, and a filtrate was partitioned between aqueous layer and organic layer. The aqueous layer was extracted with ethyl acetate. The combined organic layers were filtrated using a glass filter having silica gel laid thereon. The silica gel was washed with ethyl acetate, organic layers obtained were combined, and the solvent was evaporated under a reduced pressure. The resultant residue was purified by silica gel column chromatography (heptane:ethyl acetate=7:1 and then 4:1) to give the title compound (195 g, yield: 89%).

1. filtrationthe resultant mixture was filtrated
2. customa filtrate was partitioned between aqueous layer and organic layer
3. extractionThe aqueous layer was extracted with ethyl acetate
4. filtrationThe combined organic layers were filtrated
5. filtrationfilter
6. washThe silica gel was washed with ethyl acetate, organic layers
7. customobtained
8. customthe solvent was evaporated under a reduced pressure
9. customThe resultant residue was purified by silica gel column chromatography (heptane