Reaktion #67636

Reaktionsgleichung

toluene water

Compound 1020

2,5-dibromo-3-methoxypyridine

potassium phosphate

→

5-bromo-2-cyclopropyl-3-methoxypyridine

Ausbeute 70.0%

Lösungsmittel

EtOAc

NaCl

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeThe 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
   TemperaturThe reaction mixture was refluxed for 18 hours
4. 4
   Sonstigeresulting in a mixture of products by HPLC analysis
5. 5
   TemperaturThe reaction was cooled
6. 6
   SonstigeThe organics were separated
7. 7
   Trocknendried (MgSO4)
8. 8
   Einengenconcentrated under reduced pressure
9. 9
   Sonstigeto provide a solid, which
10. 10
    Sonstigewas purified by medium pressure silica gel chromatography (0-8% EtOAc/hexanes gradient)

Vorschrift

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.

Quelle