Iodine → 2-Fluoro-4-iodoaniline

Temperature

60 °C

2-Fluoroaniline (54 g, 486 mmol) was added to a vigorously stirred solution of sodium bicarbonate (41 g, 486 mmol) in water (250 mL). The suspension was warmed to 60° C. on an oil bath and iodine (123 g, 486 mmol) was added portion-wise. After complete addition, the dark mixture was stirred for an additional 3 h at 60° C. After cooling to rt, methylene chloride (300 mL) was added followed by saturated hydrogensulfite solution (300 mL). The biphasic system was vigorously stirred for an additional 10 min. The mixture was poured into a 2 L separatory funnel and the organic layer was released. The aqueous was further extracted with methylene chloride (3×200 mL) and the combined organics were washed with brine (200 mL) and dried over anhydrous sodium sulfate. After filtration, the solvent was removed to give a black crystalline solid. Hexane (300 mL) was added and the mixture was heated to reflux. The hexane was decanted from a black, insoluble syrup. The product crystallized from the hexane on cooling as fine yellow needles. 65 g (274 mmol) was isolated as a fine yellow solid. Yield: 56%; mp 53° C.; 1H NMR (400 MHz, CDCl3) δ 8.1 (t, J=8 Hz, 1H), 7.4 (d, J=6 Hz, 1H), 7.2 (d, J=6 Hz, 1H).

1. additionAfter complete addition
2. temperatureAfter cooling to rt
3. stirringThe biphasic system was vigorously stirred for an additional 10 min
4. additionThe mixture was poured into a 2 L separatory funnel
5. extractionThe aqueous was further extracted with methylene chloride (3×200 mL)
6. washthe combined organics were washed with brine (200 mL)
7. dry with materialdried over anhydrous sodium sulfate
8. filtrationAfter filtration
9. customthe solvent was removed
10. customto give a black crystalline solid
11. temperaturethe mixture was heated to reflux
12. customThe hexane was decanted from a black, insoluble syrup
13. customThe product crystallized from the hexane
14. temperatureon cooling as fine yellow needles
15. custom65 g (274 mmol) was isolated as a fine yellow solid

ORD record

ord-edc7c4471a3342bdbfdd0a0e41d370e1

Source dataset

uspto-grants-2006_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07101886B2