5-FLUORO-2-METHOXYPYRIDINE-3-BORONIC ACID PINACOL ESTER synthesis

Yield: 81.4%

Reaction Conditions:

with dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂;potassium acetate in 1,4-dioxane at 100; for 0.75 h;

Steps:

140 Preparation 140: 5-fluoro-2-methoxy-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine
3-Bromo-5-fluoro-2-methoxypyridine (250 mg, 1.21 mmol) was added to a stirred solution of 452 KOAc (238.2 mg, 2.42 mmol) in 115 dioxane (10 mL) followed by the addition of 456 bispinacolatodiborane (308.1 mg, 1.21 mmol). The reaction mixture was degassed with N₂ for 10 mins and PdCl₂(dppf).DCM (99.02 mg, 0.12 mmol) added and degassed for another 10 min. The reaction mixture was heated at 100° C. for 45 mins and evaporated to dryness under reduced pressure. The residue was dissolved in 50% 81 EtOAc in 82 hexane, filtered through Celite and evaporated to dryness in vacuo afford the 457 title compound (250 mg, 81.4%) which was used without further purification. LCMS m/z=254 [MH]⁺

References:

CYSTIC FIBROSIS FOUNDATION THERAPEUTICS, INC.;Strohbach, Joseph Walter;Limburg, David Christopher;Mathias, John Paul;Thorarensen, Atli;Denny, Rajiah Aldrin;Zapf, Christoph Wolfgang;Elbaum, Daniel;Gavrin, Lori Krim;Efremov, Ivan Viktorovich US2018/141954, 2018, A1 Location in patent:Paragraph 0576; 0577