Ethanol → N-(2-fluoro-4-iodophenyl)acetamide

To a stirred solution of 2-fluoro-4-iodo-phenylamine (61 g, 257 mmol) in anhydrous pyridine (25 mL) was added drop-wise acetic anhydride (32.8 mL, 321 mmol) at such a rate to maintain the internal temperature between 10° C. and 20° C. At the end of the addition, the reaction was stirred for an additional 0.5 h at rt followed by heating on an oil bath (external temperature 50–60° C.). The reaction was monitored by thin layer chromatography. Once complete (ca. 1.5 h), the mixture was cooled and the reaction mixture solidified. The solid was slurried with cold ethanol (50 mL) and filtered. The solid was washed with cold ethanol (mL) and dried to a fine white crystalline material. The filtrate was concentrated and taken up in ethanol (20 mL) and cooled overnight. Further product was obtained. 63 g (226 mmol) was isolated as a fine white, crystalline solid. Yield: 88%; mp 153° C.; 1H NMR (400 MHz, CDCl3) δ 8.15 (t, J=8 Hz, 1H), 7.33 (br s, 1H), 7.49 (m, 2H), 2.24 (s, 3H, Me).

1. temperatureto maintain the internal temperature between 10° C. and 20° C
2. additionAt the end of the addition
3. temperatureby heating on an oil bath (external temperature 50–60° C.)
4. temperatureOnce complete (ca. 1.5 h), the mixture was cooled
5. filtrationfiltered
6. washThe solid was washed with cold ethanol (mL)
7. customdried to a fine white crystalline material
8. concentrationThe filtrate was concentrated
9. temperaturecooled overnight
10. customFurther product was obtained
11. custom63 g (226 mmol) was isolated as a fine white, crystalline solid

ORD record

ord-bdac2af39b124e10ab7c6e2479d7eca8

Source dataset

uspto-grants-2006_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07101886B2