Dimethylformamide → 5-(1-Isopropyl-piperidin-4-yloxy)-1-(2,2,2-trifluoro-ethyl)-1H-indole-2-carboxylic acid ethyl ester

Participants

Reaction Conditions

Reaction Steps

To a mixture of 5-(1-isopropyl-pyrrolidin-3-yloxy)-1H-indole-2-carboxylic acid ethyl ester (intermediate, 4 g, 1.0 eq.) in dimethylformamide (40 mL) was added sodium hydride (dispersion in oil, 60% in mass, 533 mg, 1.1 eq.) in several portions. The solution was stirred 30 min at 70° C. Then 2,2,2-trifluoroethyltrifluoromethanesulfonate (3.37 g, 1.2 eq.) was added and the reaction mixture was stirred at 70° C. overnight. The reaction mixture was partitioned between an aqueous solution of sodium hydrogenocarbonate and ethyl acetate. The organic layer was washed with water and brine, evaporated in vacuo and then purified on silica eluting with dichloromethane/methanol/ammoniac. One fraction was isolated and dried in vacuo, to yield 3.9 g (78%) of the desired product as off-white solid. MS (m/e): 413.5 (MH+, 100%)

Provenance & Evidence