Potassium Carbonate → (+)-2-(4-Ethyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)-2-(2-fluoro-4-(8-fluoroquinolin-7-yl)phenyl)acetamide

Participants

Reaction Conditions

Reaction Steps

A 20 mL reaction vial equipped with a stirbar was charged with 2-(4-bromo-2-fluorophenyl)-2-(4-ethyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)acetamide (0.150 g, 0.350 mmol), bis(pinacolato)diboron (0.205 g, 0.806 mmol), PdCl2(dppf)-CH2Cl2 adduct (0.020 g, 0.025 mmol), and potassium acetate (0.076 g, 0.770 mmol). The solids were diluted with 1,4-dioxane (3.12 mL) and the reaction mixture was warmed to 90° C. with stirring overnight. The reaction mixture was then treated with PdCl2(dppf)-CH2Cl2 adduct (0.020 g, 0.025 mmol), 2M aq potassium carbonate (0.385 mL, 0.770 mmol), and 7-bromo-8-fluoroquinoline (0.091 g, 0.403 mmol), and the resulting reaction mixture was stirred at 90° C. for 1 h. The mixture was then diluted with 20 mL dichloromethane and filtered through a stacked pad of sodium sulfate over celite. The filtrate was concentrated to a residue, which was purified by silica gel flash chromatography (0.5-10% methanol:ethyl acetate). Fractions containing the desired material were pooled and concentrated to a hard lacquer and the product was resolved by chiral preparative HPLC (Chromegachiral CC4, 100% methanol) to afford the title compound in >99% ee as an off white solid (42 mg, 0.081 mmol, 23% yield). MS(ES)+ m/e 495.4 [M+H]+. αD=+40 deg (c=0.06, methanol).

Provenance & Evidence