反应详情

A stirred mixture of 19.0 grams (0.068 mole) of 4-fluoro-2-nitro-6-methylphenyl iodide and 7.0 grams (0.078 mole) of copper(I) cyanide in 100 mL of N,N-dimethylformamide was heated at 150°-155° C. for 30 minutes. The reaction mixture was then diluted with 400 mL of water and 100 mL of ethyl acetate. The mixture was filtered, and the filtrate was placed in a separatory funnel. The organic layer was separated, and the aqueous layer was washed with 200 mL of ethyl acetate. The combined wash and organic layer was then washed with three 150 mL portions of aqueous 5% lithium chloride. The mixture was dried with magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure to a residue. The residue was subjected to column chromatography on silica gel. Elution was accomplished using 1:1 methylene chloride: petroleum ether. The product-containing fractions were combined and concentrated under reduced pressure, yielding 12.8 grams of 4-fluoro-2-nitro-6-methylbenzonitrile, mp 61°-63° C. The NMR spectrum was consistent with the proposed structure. Step E Synthesis of 2-amino-4-fluoro-6-methylbenzonitrile as an intermediate

1. temperaturewas heated at 150°-155° C. for 30 minutes
2. filtrationThe mixture was filtered
3. customthe filtrate was placed in a separatory funnel
4. customThe organic layer was separated
5. washthe aqueous layer was washed with 200 mL of ethyl acetate
6. washThe combined wash
7. washorganic layer was then washed with three 150 mL portions of aqueous 5% lithium chloride
8. dry with materialThe mixture was dried with magnesium sulfate
9. filtrationfiltered
10. concentrationThe filtrate was concentrated under reduced pressure to a residue
11. washElution
12. concentrationconcentrated under reduced pressure