2-Chloro-4-iodoaniline → 3-[(2-Chloro-4-iodophenyl)amino]isonicotinic acid

To suspension of 3-fluoroisonicotinic acid (2.00 g, 14.17 mmol, in tetrahydrofuran (50 ml) at −78° C. was added lithium bis(trimethylsilyl)amide (14.3 ml, 17.01 mmol). The dark colored suspension was stirred for 15 min. In another flask, to a solution of 2-chloro-4-iodoaniline (4.7 g, 18.43 mmol) in THF (50 ml) was added lithium bis(trimethylsilyl)amide (24.9 ml, 29.77 mmol) at −78° C. under N2. The resulting green colored solution was stirred for 15 min. To this green colored solution the lithiated acid solution was added. The cold bath was removed, allowed to warm to room temperature, and stirred overnight. The mixture was filtered, and the crude was diluted with EtOAc (400 ml). It was then washed with dilute HCl (25 ml), H2O (25 ml), and dried. During concentration of the solvent, 3-[(2-chloro-4-iodophenyl)amino]isonicotinic acid was separated out as an yellow solid. (1.3 g, 24%)

1. stirringThe resulting green colored solution was stirred for 15 min
2. additionTo this green colored solution the lithiated acid solution was added
3. customThe cold bath was removed
4. stirringstirred overnight
5. filtrationThe mixture was filtered
6. additionthe crude was diluted with EtOAc (400 ml)
7. washIt was then washed with dilute HCl (25 ml), H2O (25 ml)
8. customdried
9. customDuring concentration of the solvent, 3-[(2-chloro-4-iodophenyl)amino]isonicotinic acid was separated out as an yellow solid

ORD record

ord-23b0b8c07ba843b6af0aaf18ece7b1a3

Source dataset

uspto-grants-2014_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08841459B2