Reacción #67636

Ecuación de reacción

toluene water

Compound 1020

2,5-dibromo-3-methoxypyridine

potassium phosphate

→

5-bromo-2-cyclopropyl-3-methoxypyridine

Rendimiento 70.0%

Disolventes

EtOAc

NaCl

Condiciones de reacción

Tratamiento posterior

1. 1
   OtroThe reaction mixture was flushed with nitrogen gas for 10 minutes
2. 2
   workup.ADDITIONPd(PPh3)4 (1.4 g, (1.21 mmol) was added
3. 3
   TemperaturaThe reaction mixture was refluxed for 18 hours
4. 4
   Otroresulting in a mixture of products by HPLC analysis
5. 5
   TemperaturaThe reaction was cooled
6. 6
   OtroThe organics were separated
7. 7
   Secadodried (MgSO4)
8. 8
   Concentraciónconcentrated under reduced pressure
9. 9
   Otroto provide a solid, which
10. 10
    Otrowas purified by medium pressure silica gel chromatography (0-8% EtOAc/hexanes gradient)

Procedimiento

As shown in step 6-v of Scheme 6, Compound 1020 (3.6 g, 13.5 mmol), potassium cyclopropyl-trifluoro-boron (2.5 g, 16.9 mmol), and potassium phosphate (8.6 g, 40.5 mmol) were taken up in about 80 mL of a toluene/water mixture. The reaction mixture was flushed with nitrogen gas for 10 minutes and Pd(PPh3)4 (1.4 g, (1.21 mmol) was added. The reaction mixture was refluxed for 18 hours, resulting in a mixture of products by HPLC analysis. The reaction was cooled, diluted with EtOAc and saturated NaCl. The organics were separated, dried (MgSO4), and concentrated under reduced pressure to provide a solid, which was purified by medium pressure silica gel chromatography (0-8% EtOAc/hexanes gradient) to give 5-bromo-2-cyclopropyl-3-methoxypyridine (Compound 1022, 0.54 g, 70% pure): ESMS (M+H) 227.9/229.9. This compound was used as is in subsequent reactions.

Fuente