Reacción #67796

Ecuación de reacción

lithium bis(trimethylsilyl)amide

3-fluoroisonicotinic acid

2-chloro-4-iodoaniline

lithium bis(trimethylsilyl)amide

→

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

Disolventes

tetrahydrofuran

THF

Condiciones de reacción

Tratamiento posterior

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
   OtroThe cold bath was removed
4. 4
   workup.STIRRINGstirred overnight
5. 5
   FiltraciónThe mixture was filtered
6. 6
   workup.ADDITIONthe crude was diluted with EtOAc (400 ml)
7. 7
   LavadoIt was then washed with dilute HCl (25 ml), H2O (25 ml)
8. 8
   Otrodried
9. 9
   OtroDuring concentration of the solvent, 3-[(2-chloro-4-iodophenyl)amino]isonicotinic acid was separated out as an yellow solid

Procedimiento

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%)

Fuente