반응 #67636

반응 방정식

toluene water

Compound 1020

2,5-dibromo-3-methoxypyridine

potassium phosphate

→

5-bromo-2-cyclopropyl-3-methoxypyridine

수율 70.0%

용매

EtOAc

NaCl

반응 조건

후처리

1. 1
   기타The 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
   온도The reaction mixture was refluxed for 18 hours
4. 4
   기타resulting in a mixture of products by HPLC analysis
5. 5
   온도The reaction was cooled
6. 6
   기타The organics were separated
7. 7
   건조dried (MgSO4)
8. 8
   농축concentrated under reduced pressure
9. 9
   기타to provide a solid, which
10. 10
    기타was purified by medium pressure silica gel chromatography (0-8% EtOAc/hexanes gradient)

실험 절차

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.

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