تفاعل #67636

معادلة التفاعل

toluene water

Compound 1020

2,5-dibromo-3-methoxypyridine

potassium phosphate

→

5-bromo-2-cyclopropyl-3-methoxypyridine

المردود 70.0%

المذيبات

EtOAc

NaCl

ظروف التفاعل

المعالجة

1. 1
   أخرىThe 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
   درجة الحرارةThe reaction mixture was refluxed for 18 hours
4. 4
   أخرىresulting in a mixture of products by HPLC analysis
5. 5
   درجة الحرارةThe reaction was cooled
6. 6
   أخرىThe organics were separated
7. 7
   تجفيفdried (MgSO4)
8. 8
   تركيزconcentrated under reduced pressure
9. 9
   أخرىto provide a solid, which
10. 10
    أخرىwas purified by medium pressure silica gel chromatography (0-8% EtOAc/hexanes gradient)

الإجراء التجريبي

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.

المصدر