Reacción #48310

Ecuación de reacción

2,6-difluoro-3-iodopyridine

NH4Cl

neopentylmagnesium chloride

ether

→

2,6-difluoro-3-neopentylpyridine

Disolventes

THF

THF

Condiciones de reacción

Tratamiento posterior

1. 1
   TemperaturaAfter cooling
2. 2
   OtroThe cooling bath was removed
3. 3
   workup.ADDITIONwas added dropwise
4. 4
   workup.STIRRINGAfter stirring overnight the reaction
5. 5
   Temperaturato cool
6. 6
   OtroThe reaction mixture was partitioned between EtOAc/Water
7. 7
   ExtracciónThe aqueous layer was extracted with EtOAc (50 mL)
8. 8
   Lavadothe combined organic layers washed with brine
9. 9
   Concentraciónconcentrated in vacuo
10. 10
    Otrochromatographed through a Redi-Sep® pre-packed silica gel column (40 g)
11. 11
    Lavadoeluting with 1% EtOAc in hexane

Procedimiento

To a 500 mL RBF was added neopentylmagnesium chloride, 111.0M in ether (28.0 ml, 28 mmol) and an ice bath. After cooling, zinc(II) chloride, 0.5M in THF (56.0 ml, 28 mmol) was added dropwise. The cooling bath was removed and after stirring for 45 minutes, Reactant 1 (0.26 g, 0.32 mmol) was added followed by 2,6-difluoro-3-iodopyridine (2.74 g, 8.0 mmol) in THF (10 mL), which was added dropwise. The yellow solution was then heated to 60° C. After stirring overnight the reaction was allowed to cool and sat'd. NH4Cl was added cautiously. The reaction mixture was partitioned between EtOAc/Water. The aqueous layer was extracted with EtOAc (50 mL) and the combined organic layers washed with brine and concentrated in vacuo. The crude product was adsorbed onto a plug of silica gel and chromatographed through a Redi-Sep® pre-packed silica gel column (40 g), eluting with 1% EtOAc in hexane, to provide 2,6-difluoro-3-neopentylpyridine as a colorless oil. MS m/z: 186 (M+1).

Fuente