Boron tribromide → HCID 67383094, compound

Participants

Reaction Steps

(5-Bromo-2-fluorophenyl)(2-fluoro-3-(methoxymethoxy)-6-(tetrahydro-2H-pyran-4-yl)pyridin-4-yl)methanol (0.84 g, 1.90 mmol) was dissolved in DCM (30 mL) and treated with 4-methylmorpholine 4-oxide (0.56 g, 4.74 mmol). Once the reagent had dissolved tetrapropylammonium perruthenate (0.033 g, 0.095 mmol) was added and the pale yellow solution stirred at RT. After 10 min the mixture had turned dark. Additional DCM (50 mL) was added followed by water (50 mL) and saturated ammonium chloride (50 mL). The phases were mixed and separated and the organic dried with magnesium sulfate before evaporating to dryness under reduced pressure. The crude was redissolved in dichloromethane (25 mL) and cooled in an ice bath under nitrogen. Boron tribromide (neat, 0.25 mL, 2.64 mmol) was added and the mixture turned orange yellow. After 10 min saturated sodium bicarbonate (70 mL) and DCM (100 mL) were added. The phases were mixed and separated and the organic dried with magnesium sulfate before evaporating to dryness under reduced pressure. The crude was treated with excess cesium carbonate (1.2 g) and ACN (50 mL) and stirred at room temperature for 10 min. The mixture was evaporated to dryness under reduced pressure. The crude product was partitioned between DCM (100 mL) and water (100 mL). The organic was dried with magnesium sulfate and evaporated to dryness under reduced pressure to give 7-bromo-1-fluoro-3-(tetrahydro-2H-pyran-4-yl)-5H-chromeno[2,3-c]pyridin-5-one (0.645 g, 1.705 mmol, 90% yield) as a white solid. It was used without purification.

Provenance & Evidence