Tetrafluoroterephthalonitrile → 3-Amino-4,6,7-trifluoro-1,2-benzisoxazole-5-carbonitrile

To a stirring solution of N,N-diisopropylethylamine (19.2 g, 110 mmol) in CH3CN (100 mL) was added acetone oxime (8 g, 110 mmol). After stirring for 30 min, a solution of tetrafluoroterephthalonitrile (20 g, 100 mmol) in CH3CN (50 mL) was added; and the mixture was stirred overnight. Saturated aqueous ammonium chloride (100 mL) was added and the solvents were removed in vacuo. The residue was partitioned between EtOAc and brine. The layers were separated and the organic phase was washed once with brine, dried (MgSO4), filtered and concentrated. This crude solid was suspended in EtOH (150 mL) and concentrated HCl (50 mL) and water (100 mL) were added. This was refluxed for 3 h. After cooling to room temperature, the solvents were removed in vacuo. The residue was treated with saturated aqueous sodium bicarbonate (200 mL), and the product was extracted by washing the aqueous layer three times with EtOAc. This organic solution was washed once with brine, dried (MgSO4), filtered and concentrated to give a yellow solid. The crude product was purified by silica gel chromatography, eluting with a gradient of hexanes to 40% EtOAc/hexanes (9.2 g, 43%).

1. stirringand the mixture was stirred overnight
2. customthe solvents were removed in vacuo
3. customThe residue was partitioned between EtOAc and brine
4. customThe layers were separated
5. washthe organic phase was washed once with brine
6. dry with materialdried (MgSO4)
7. filtrationfiltered
8. concentrationconcentrated
9. additionconcentrated HCl (50 mL) and water (100 mL) were added
10. temperatureThis was refluxed for 3 h
11. customthe solvents were removed in vacuo
12. additionThe residue was treated with saturated aqueous sodium bicarbonate (200 mL)
13. extractionthe product was extracted
14. washby washing the aqueous layer three times with EtOAc
15. washThis organic solution was washed once with brine
16. dry with materialdried (MgSO4)
17. filtrationfiltered
18. concentrationconcentrated
19. customto give a yellow solid
20. customThe crude product was purified by silica gel chromatography
21. washeluting with a gradient of hexanes to 40% EtOAc/hexanes (9.2 g, 43%)

ORDレコード

ord-dbf94a16b655471d89f6f8c3e779b73f

出典データセット

uspto-grants-1999_12

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US06008367