Reacción #662801

Ecuación de reacción

K3PO4

2-chloro-4-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine

2-bromo-1-(2,4-difluorophenoxy)-4-nitrobenzene

tricyclohexylphosphine

→

2-chloro-5-[2-(2,4-difluorophenoxy)-5-nitrophenyl]-4-fluoropyridine

Rendimiento 57.3%

Disolventes

1,4-dioxane

Condiciones de reacción

Tratamiento posterior

1. 1
   Otromicrowave irradiation (normal) for 45 min
2. 2
   OtroThe crude reaction mixture
3. 3
   Filtraciónwas filtered through a short plug of celite
4. 4
   Lavadothe celite plug was washed with EtOAc (˜50 mL)
5. 5
   LavadoThe filtrate was washed with water (2×30 mL), brine
6. 6
   Secadodried over sodium sulfate
7. 7
   Filtraciónfiltered
8. 8
   Concentraciónconcentrated in vacuo
9. 9
   OtroThe resulting residue was purified by silica gel column chromatography (12 g ISCO, gradient 05-75% EtOAc in hexanes)

Procedimiento

A mixture of 2-chloro-4-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (170 mg, 0.66 mmol), 2-bromo-1-(2,4-difluorophenoxy)-4-nitrobenzene (326 mg, 0.98 mmol), Pd2(dba)3 (30 mg, 5%), and tricyclohexylphosphine (280 mg, 10%) was suspended in 1,4-dioxane (4 mL) and aqueous 1M K3PO4 (2 mL). The mixture was heated to 70° C. using microwave irradiation (normal) for 45 min. The crude reaction mixture was filtered through a short plug of celite and the celite plug was washed with EtOAc (˜50 mL). The filtrate was washed with water (2×30 mL), brine, dried over sodium sulfate, filtered and concentrated in vacuo. The resulting residue was purified by silica gel column chromatography (12 g ISCO, gradient 05-75% EtOAc in hexanes) to afford the free base of the desired product, 2-chloro-5-[2-(2,4-difluorophenoxy)-5-nitrophenyl]-4-fluoropyridine as a yellow solid (144 mg, 57%). LCMS (M+H)+=381.

Fuente