反应详情

温度

60 °C

To a solution of 2-bromo-3-fluoro-6-methylpyridine (1.0 equiv.) in THF and Water (10:1, 0.2 M) was added 2,6-difluorophenylboronic acid (2.0 equiv.) and potassium fluoride (3.3 equiv.). The reaction was degassed for 10 minutes, then Pd2(dba)3 (0.05 equiv.) was added, followed by tri-t-butylphosphine (0.1 equiv.). The reaction was stirred to 60° C. for 1 hour at which point, all starting material was consumed as indicated by LC/MS. The reaction was allowed to cool to room temperature, partitioned with ethyl acetate and water, the organic phase was dried with sodium sulfate, filtered, and concentrated. The crude material was diluted in EtOH to 0.1 M, and 0.5 equiv. of NaBH4 was added to reduce the dba. The reaction was stirred for one hour at room temperature, then quenched with water and concentrated under vacuo to remove the ethanol. The product was extracted in ether, washed with brine, the organics were dried over sodium sulfate, filtered, and concentrated. The crude material was loaded on silica gel and purified via column chromatography (ISCO) eluting with hexanes and ethyl acetate (0%-10% ethyl acetate). The pure fractions were combined, and concentrated to yield 2-(2,6-difluorophenyl)-3-fluoro-6-methylpyridine as a light yellow oil in 86% yield. LC/MS=224.0 (M+H), Rt=0.84 min.

1. customThe reaction was degassed for 10 minutes
2. customall starting material was consumed
3. temperatureto cool to room temperature
4. custompartitioned with ethyl acetate and water
5. dry with materialthe organic phase was dried with sodium sulfate
6. filtrationfiltered
7. concentrationconcentrated
8. additionwas added
9. stirringThe reaction was stirred for one hour at room temperature
10. customquenched with water
11. concentrationconcentrated under vacuo
12. customto remove the ethanol
13. extractionThe product was extracted in ether
14. washwashed with brine
15. dry with materialthe organics were dried over sodium sulfate
16. filtrationfiltered
17. concentrationconcentrated
18. custompurified via column chromatography (ISCO)
19. washeluting with hexanes and ethyl acetate (0%-10% ethyl acetate)
20. concentrationconcentrated