Potassium Phosphate, Tribasic → 5-Bromo-2-cyclopropyl-3-methoxypyridine

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.

1. customThe reaction mixture was flushed with nitrogen gas for 10 minutes
2. additionPd(PPh3)4 (1.4 g, (1.21 mmol) was added
3. temperatureThe reaction mixture was refluxed for 18 hours
4. customresulting in a mixture of products by HPLC analysis
5. temperatureThe reaction was cooled
6. customThe organics were separated
7. dry with materialdried (MgSO4)
8. concentrationconcentrated under reduced pressure
9. customto provide a solid, which
10. customwas purified by medium pressure silica gel chromatography (0-8% EtOAc/hexanes gradient)

ORD-Eintrag

ord-5572f7d79e614a3186d3b1809bed68ec

Quelldatensatz

uspto-grants-2013_09

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08524906B2