Reaction #67796

Reaction equation

lithium bis(trimethylsilyl)amide

3-fluoroisonicotinic acid

2-chloro-4-iodoaniline

lithium bis(trimethylsilyl)amide

→

3-[(2-chloro-4-iodophenyl)amino]isonicotinic acid

Solvents

tetrahydrofuran

THF

Conditions

Workup

1. 1
   workup.STIRRINGThe resulting green colored solution was stirred for 15 min
2. 2
   workup.ADDITIONTo this green colored solution the lithiated acid solution was added
3. 3
   OtherThe cold bath was removed
4. 4
   workup.STIRRINGstirred overnight
5. 5
   FiltrationThe mixture was filtered
6. 6
   workup.ADDITIONthe crude was diluted with EtOAc (400 ml)
7. 7
   WashIt was then washed with dilute HCl (25 ml), H2O (25 ml)
8. 8
   Otherdried
9. 9
   OtherDuring concentration of the solvent, 3-[(2-chloro-4-iodophenyl)amino]isonicotinic acid was separated out as an yellow solid

Procedure

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%)

Source