Ethyl Acetate → 3-Chloro-2-isobutylpyridine

Temperature

75 °C

3-Chloro-2-iodopyridine (1.552 g, 6.482 mmol), isobutylboronic acid (0.725 g, 7.112 mmol), potassium carbonate (2.7 g, 0.0195 mol) and silver oxide (3.8 g, 0.0164 mol) were suspended in THF (25 mL). The mixture was degassed three times and 1,1-Bis(diphenylphosphino)ferrocene-palladium(11)dichloride dichloromethane (1:1) (0.520 g, 0.637 mmol) was added. The reaction mixture was heated at 75° C. under nitrogen for seven hours. The mixture was diluted EtOAc (15 mL) and washed with an aqueous solution of hydrochloric acid (2.0 M, 2×15 mL). The organic layer was discarded and the aqueous layer basified with careful addition of a saturated aqueous solution of sodium hydrogen carbonate (50 mL). The product was extracted with EtOAc (2×15 mL). The organics were combined, dried over sodium sulfate, filtered, and concentrated in vacuo. The resulting crude was purified by silica gel chromatography eluting with 0 to 5% EtOAc in heptane to yield the title compound as a colourless oil (0.582 g, 53% yield).

1. additionwas added
2. washwashed with an aqueous solution of hydrochloric acid (2.0 M, 2×15 mL)
3. additionthe aqueous layer basified with careful addition of a saturated aqueous solution of sodium hydrogen carbonate (50 mL)
4. extractionThe product was extracted with EtOAc (2×15 mL)
5. dry with materialdried over sodium sulfate
6. filtrationfiltered
7. concentrationconcentrated in vacuo
8. customThe resulting crude was purified by silica gel chromatography
9. washeluting with 0 to 5% EtOAc in heptane

ORD record

ord-94c132b5a8da4480a8846bdcc8b51bd4

Source dataset

uspto-grants-2013_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08592629B2