Potassium Phosphate, Tribasic → 3-Chloro-2-cyclopropylpyridine

온도

100 °C

3-Chloro-2-bromopyridine (5.0 g, 26 mmol) and potassium phosphate tribasic (19.3 g, 90.9 mmol) were suspended in toluene (40.0 mL) and water (2.0 mL). The mixture was sonicated for 10 minutes, then cyclopropylboronic acid (1.12 g, 13.0 mmol), palladium diacetate (0.093 g, 0.414 mmol) and tricyclohexylphosphine (0.243 g, 0.867 mmol) were added to the reaction mixture, which was heated into a pre heated DrySyn® at 100° C., under a nitrogen atmosphere for 2 hours. Then cyclopropylboronic acid (1.12 g, 13.0 mmol), palladium diacetate (0.093 g, 0.414 mmol) and tricyclohexylphosphine (0.243 g, 0.867 mmol) were added to the reaction mixture and the mixture was stirred for 2 hours. Then cyclopropylboronic acid (1.12 g, 13.0 mmol), palladium diacetate (0.093 g, 0.414 mmol) and tricyclohexylphosphine (0.243 g, 0.867 mmol) were added to the reaction mixture and the mixture was stirred for 2 hours more. The reaction mixture was stirred at room temperature for 16 hours, diluted with EtOAc (40.0 mL) and water (40.0 mL) and filtered on a pad of Arbocel® under a stream of nitrogen. The organic layer was separated and washed with aqueous citric acid (10%, 3×25.0 mL), followed by aqueous hydrochloric acid (1 M, 3×20.0 mL). The organic layer was discarded and the aqueous layer basified again with careful addition of a saturated aqueous solution of sodium hydrogen carbonate (100.0 mL). The product was extracted with TBME (3×20.0 mL). The combined organics were washed once more with aqueous citric acid (10%, 25.0 mL). The organic layer was then dried over sodium sulfate, filtered, and concentrated in vacuo to yield the title compound as a pale brown oil (2.45 g, 16.02 mmol, 62%).

1. customThe mixture was sonicated for 10 minutes
2. temperaturewas heated into a pre
3. stirringthe mixture was stirred for 2 hours more
4. stirringThe reaction mixture was stirred at room temperature for 16 hours
5. filtrationfiltered on a pad of Arbocel® under a stream of nitrogen
6. customThe organic layer was separated
7. washwashed with aqueous citric acid (10%, 3×25.0 mL)
8. additionthe aqueous layer basified again with careful addition of a saturated aqueous solution of sodium hydrogen carbonate (100.0 mL)
9. extractionThe product was extracted with TBME (3×20.0 mL)
10. washThe combined organics were washed once more with aqueous citric acid (10%, 25.0 mL)
11. dry with materialThe organic layer was then dried over sodium sulfate
12. filtrationfiltered
13. concentrationconcentrated in vacuo

ORD 기록

ord-3a610a06828542e3b374138f2fdd5914

출처 데이터셋

uspto-grants-2015_08

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US09102621B2