Hydrochloric Acid → 1-{3-Fluoro-4-[(phenylmethyl)oxy]phenyl}-6-methyl-1h-indazol-4-ol

Participants

Reaction Steps

A solution of 4-bromo-1-{3-fluoro-4-[(phenylmethyl)oxy]phenyl}-6-methyl-1H-indazole (D12) (1.97 g, 4.5 mmol) and KOH (1 g, 18 mmol) in dioxane (50 mL) and water (50 mL) was sonicated under a flow of argon for 5 minutes after which the bis(1,1-dimethylethyl)[2′,4′,6′-tris(1-methylethyl)-2-biphenylyl]phosphane (115 mg, 0.27 mmol) and Pd2 dba3 (82 mg, 0.09 mmol) were added and it was heated to reflux for 2 hours. The mixture was then cooled to room temperature, diluted with EtOAc and water and the pH was adjusted to circa 7 with 1M HCl. The phases were separated, the aqueous re-extracted with EtOAc and the combined organics were finally dried over MgSO4. The crude material (2.1 g) was purified by flash chromatography (Biotage SP4, 40+M silica column) with a gradient of EtOAc 0 to 50% in hexane to afford 730 mg of desired compound (D13).

Provenance & Evidence