Dichloromethane → 2-fluoro-6-(tetrahydro-2H-pyran-4-yl)pyridin-3-ol

Participants

Reaction Conditions

Reaction Steps

6-Bromo-2-fluoropyridin-3-ol (3.67 g, 19.12 mmol), 2-(3,6-dihydro-2H-pyran-4-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (4.02 g, 19.12 mmol), potassium phosphate (6.25 g, 29.4 mmol), and 1,1-bis[(di-t-butyl-p-methylaminophenyl]palladium(ii) chloride (0.23 g, 0.33 mmol) were suspended in a mixture of dioxane (5 mL) and water (0.5 mL) and heated in the microwave to 110° C. for 20 min. The phases were allowed to settle and the organic evaporated to dryness under reduced pressure. Purification using silica chromatography (hexane to EtOAc gradient) gave the desired coupled material. It was dissolved in MeOH (60 mL) and DCM (30 mL) and treated with palladium (10% wt on carbon, 0.26 g, 0.24 mmol) and hydrogenated at 60 psi overnight. The mixture was filtered through a pad of celite and the filtrate evaporated under reduced pressure to give the desired 2-fluoro-6-(tetrahydro-2H-pyran-4-yl)pyridin-3-ol (1.92 g, 9.74 mmol, 50.9% yield). It was used without purification.

Provenance & Evidence