Sodium Carbonate → 6-(4-(Methylsulfonyl)phenyl)pyridin-3-ol

Participants

Reaction Conditions

Reaction Steps

A mixture of 6-bromo-3-pyridinol (1.28 g, 7.35 mmol), [4-(methylsulfonyl)phenyl]boronic acid (1.47 g, 7.35 mmol), and 2M Na2CO3 (5 mL) in DMF (15 mL) was treated with PdCl2(PPh3)2 (0.52 g, 0.74 mmol) and the mixture was heated at 50° C. overnight. The reaction was treated with additional catalyst (PdCl2(PPh3)2, 0.26 g, 0.37 mmol) and was heated at 50° C. overnight, then was heated at 90° C. overnight. The reaction was allowed to cool to room temperature and was diluted with EtOAc and water and the aqueous layer was extracted with EtOAc. The combined organic extracts were dried over MgSO4, filtered and concentrated. The resulting residue was treated with MeOH and cooled in an ice bath. The resulting precipitate was collected, washed with cold MeOH and air-dried and the filtrates were combined and set aside. The resulting tan solid was dissolved in 10% MeOH/CH2Cl2 and loaded onto a 220 g silica column, which was eluted with 1 to 5% MeOH/CH2Cl2 over 30 min, followed by 5% MeOH/CH2Cl2 for 30 min to provide 6-[4-(methylsulfonyl)phenyl]-3-pyridinol (0.36 g, 20%) as a tan solid. The mother liquors from the MeOH trituration step were concentrated and purified by chromatography 1 to 5% MeOH/CH2Cl2 over 20 min to provide additional product (0.24 g, 33% overall yield) as a tan solid.

Provenance & Evidence