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

Participants

Reaction Conditions

Reaction Steps

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%).

Provenance & Evidence