Potassium Phosphate, Tribasic → HCID 58042442, compound

Temperature

100 °C

3-Chloro-2-bromopyridine (5.0 g, 26.0 mmol) and potassium phosphate tribasic (19.3 g, 90.9 mmol) were suspended in toluene (40 mL) and water (2 mL). The reaction mixture was sonicated for 10 minutes, and then cyclopropylboronic acid (1.12 g, 13.0 mmol), palladium acetate (0.093 g, 0.414 mmol) and tricyclohexylphosphine (0.243 g, 0.867 mmol) were added to the reaction mixture, which was then placed in a pre heated DrySyn® bath at 100° C. The reaction mixture was then left to stir under nitrogen for two hours. Additional cyclopropylboronic acid (1.12 g, 13.0 mmol), palladium acetate (0.093 g, 0.414 mol) and tricyclohexylphosphine (0.243 g, 0.867 mmol) were added to the reaction mixture which was stirred for a further two hours. Additional cyclopropylboronic acid (1.12 g, 13.0 mmol), palladium acetate (0.093 g, 0.414 mmol) and tricyclohexylphosphine (0.243 g, 0.867 mmol) were again added to the reaction mixture which was stirred for a further two hours. The mixture was then left to stir at room temperature for 16 hours. The reaction mixture was diluted in ethyl acetate (40 mL) and water (40 mL) and was filtered on a pad of Arbocel® under a stream of nitrogen. The organic layer was then separated and washed three times with a 10% solution of aqueous citric acid (25 mL). The organic layer was discarded and the aqueous layer brought back to basic pH with careful addition of a saturated aqueous solution of sodium hydrogen carbonate (100 mL). The product was extracted three times with tert-butyl methyl ether (20 mL). The organic layers were combined, then dried over sodium sulfate, filtered, and concentrated in vacuo. The title compound was isolated as an orange oil (0.66 g, 16%):

1. customThe reaction mixture was sonicated for 10 minutes
2. waitThe reaction mixture was then left
3. stirringwas stirred for a further two hours
4. stirringwas stirred for a further two hours
5. waitThe mixture was then left
6. stirringto stir at room temperature for 16 hours
7. filtrationwater (40 mL) and was filtered on a pad of Arbocel® under a stream of nitrogen
8. customThe organic layer was then separated
9. washwashed three times with a 10% solution of aqueous citric acid (25 mL)
10. additionthe aqueous layer brought back to basic pH with careful addition of a saturated aqueous solution of sodium hydrogen carbonate (100 mL)
11. extractionThe product was extracted three times with tert-butyl methyl ether (20 mL)
12. dry with materialdried over sodium sulfate
13. filtrationfiltered
14. concentrationconcentrated in vacuo

ORD record

ord-87adb60651214e989d23e2d1e0954890

Source dataset

uspto-grants-2015_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09102621B2