Argon was bubbled through a suspension of 2-(4-bromo-2-fluorophenyl)-2-(4-cyclopropyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undec-9-yl)acetamide (4.61 mmol), 7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)quinoline (5.76 mmol), PdCl2(dppf)-CH2Cl2 adduct (0.138 mmol), and 2.0 M aqueous potassium carbonate (18.44 mmol) in 1,4-dioxane (36.9 mL) for 10 minutes then the reaction was heated at 100° C. for 2 hours. The reaction was cooled, treated with silica powder (˜10 g) then evaporated under reduced pressure to dryness. Purification of the residue on silica gel by flash chromatography (ethyl acetate, then 10% methanol/ethyl acetate) followed by combination of the product fractions and concentration to a residue that was taken into dichloromethane, filtered through celite, and concentrated in vacuo afforded the title product racemate (2.27 g, 91% yield) as a light tan solid. MS(ES)+ m/e 489.5 [M+H]+. Chiral resolution of the racemate by chiral HPLC (Chromegachiral CC4, methanol) gave the title product as a light yellow foam (1.0 g, 45%). This solid was triturated with hot 3,3-dimethyl-2-butanone (10 mL) with ultrasonification for 5 minutes. The suspension was cooled to room temperature and the solids were filtered then vacuum dried to afford the title compound as an off white solid in 100% ee (770 mg, 34%). MS(ES)+ m/e 489.4 [M+H]+. αD=+43 deg (c=0.2, methanol).
