Реакция #48310

Уравнение реакции

2,6-difluoro-3-iodopyridine

NH4Cl

neopentylmagnesium chloride

ether

→

2,6-difluoro-3-neopentylpyridine

Растворители

THF

THF

Условия реакции

Обработка

1. 1
   ТемператураAfter cooling
2. 2
   ДругоеThe cooling bath was removed
3. 3
   workup.ADDITIONwas added dropwise
4. 4
   workup.STIRRINGAfter stirring overnight the reaction
5. 5
   Температураto cool
6. 6
   ДругоеThe reaction mixture was partitioned between EtOAc/Water
7. 7
   ЭкстракцияThe aqueous layer was extracted with EtOAc (50 mL)
8. 8
   Промывкаthe combined organic layers washed with brine
9. 9
   Концентрированиеconcentrated in vacuo
10. 10
    Другоеchromatographed through a Redi-Sep® pre-packed silica gel column (40 g)
11. 11
    Промывкаeluting with 1% EtOAc in hexane

Методика

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).

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