Reaction #67636

Reaction equation

toluene water

Compound 1020

2,5-dibromo-3-methoxypyridine

potassium phosphate

→

5-bromo-2-cyclopropyl-3-methoxypyridine

Yield 70.0%

Solvents

EtOAc

NaCl

Conditions

Workup

1. 1
   OtherThe 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
   TemperatureThe reaction mixture was refluxed for 18 hours
4. 4
   Otherresulting in a mixture of products by HPLC analysis
5. 5
   TemperatureThe reaction was cooled
6. 6
   OtherThe organics were separated
7. 7
   Dryingdried (MgSO4)
8. 8
   Concentrationconcentrated under reduced pressure
9. 9
   Otherto provide a solid, which
10. 10
    Otherwas purified by medium pressure silica gel chromatography (0-8% EtOAc/hexanes gradient)

Procedure

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.

Source