Water → 3-Bromo-5-fluoro-2-methyl pyridine

Temperatur

110 °C

2,3-Dibromo-5-fluoropyridine (5.0 g, 19.6 mmol), Pd(PPh3)4 (1.13 g, 0.98 mmol) and methyl boronic acid (3.52 g, 58.9 mmol) were combined in dioxane (50 mL) then treated with K2CO3 (8.13, 58.9 mmol) and water (10 mL). The mixture was purged with N2 then heated to 110° C. in a sealed vessel for 16 hours. The cooled mixture was partitioned between water (100 mL) and EtOAc (50 mL) and the layers separated. The aqueous layer was extracted with EtOAc (2×50 mL) and the combined organic phases were washed with brine (50 mL), dried over Na2SO4, filtered and concentrated. The residue was purified by silica gel column chromatography eluting with 1-3% EtOAc/hexanes to afford the product as a white solid (1.20 g, 32% yield). MS (apci) m/z=190.2 (M+).

1. customThe mixture was purged with N2
2. customThe cooled mixture was partitioned between water (100 mL) and EtOAc (50 mL)
3. customthe layers separated
4. extractionThe aqueous layer was extracted with EtOAc (2×50 mL)
5. washthe combined organic phases were washed with brine (50 mL)
6. dry with materialdried over Na2SO4
7. filtrationfiltered
8. concentrationconcentrated
9. customThe residue was purified by silica gel column chromatography
10. washeluting with 1-3% EtOAc/hexanes

ORD-Eintrag

ord-bf065f4376e44ae3b8dc28b978f251c0

Quelldatensatz

uspto-grants-2014_07

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08791123B2