1,4-Dioxane → 1-((3R,4R)-3-hydroxy-4-(4-methoxy-6-methylquinolin-2-ylamino)pyrrolidin-1-yl)-2-(4-trifluoromethoxyphenyl)ethanone

Participants

Reaction Conditions

Reaction Steps

To a mixture of 2-chloro-4-methoxy-6-methylquinoline (0.12 g), Pd2(dba)3 (0.027 g), (±)-BINAP (0.056 g), 1-((3R,4R)-3-amino-4-hydroxypyrrolidin-1-yl)-2-(4-trifluoromethoxyphenyl)ethanone (0.22 g), and 1,4-dioxane (2 mL) was added sodium t-butoxide (0.17 g) under nitrogen atmosphere, and the mixture was stirred at 70° C. for 1 h. The reaction mixture was diluted with ethyl acetate and water, then the interlayer was removed by Celite filtration, and the organic layer was washed with saturated brine. The organic layer was dried with anhydrous magnesium sulfate, the desiccant was removed by filtration, the filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (silica gel, ethyl acetate, and NH silica gel, ethyl acetate/chloroform) to obtain white solid 1-((3R,4R)-3-hydroxy-4-(4-methoxy-6-methylquinolin-2-ylamino)pyrrolidin-1-yl)-2-(4-trifluoromethoxyphenyl)ethanone (0.16 g).

Provenance & Evidence