Triethylamine → 2-[3-(5-Fluoro-1h-indol-3-ylmethyl)-azetidin-1-ylmethyl]-8-methyl-2,3-dihydro-[1,4]dioxino[2,3-f]quinoline

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Reaction Steps

A solution of (2R)-4-bromobenzenesulfonic acid 8-methyl-2,3-dihydro-[1,4]dioxino[2,3-f]quinolin-2-ylmethyl ester (0.35 g,.0.80 mmol), 3-azetidin-3-ylmethyl-5-fluoro-1H-indole (0.19 g, 0.96 mmol) and triethylamine (0.16 mL, 1.2 mmol) in dimethylsulfoxide (20 mL) was heated at 90° C. under nitrogen overnight. The reaction mixture was quenched with 1N sodium hydroxide and extracted with methylene chloride (3×80 mL). The organic layer was washed with water (3×50 mL), dried over anhydrous sodium sulfate, filtered, and concentrated in vacuum. The resulting crude oil was column chromatographed on silica gel (3% methanol-ethyl acetate). The product-containing fractions were concentrated in vacuum to give 0.090 g of the (S)-enantiomer of the title compound as a brown oil. The dihydrochloride salt was prepared in ethyl acetate and collected as 0.068 g of a yellow solid, m.p. 125° C. (dec).

Provenance & Evidence