Potassium Iodide → (2S,4S)-1-[2-[(4-ethoxycarbonylbicyclo[2.2.2]oct-1-yl)amino]acetyl]-4-fluoropyrrolidine-2-carboxamide

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Reaction Steps

Ethyl 4-aminobicyclo[2.2.2]octane-1-carboxylate hydrochloride (68.8 g), potassium carbonate (77.6 g), potassium iodide (46.6 g) and N,N-dimethylformamide (167 mL) were mixed, and (2S,4S)-1-(chloroacetyl)-4-fluoropyrrolidine-2-carboxamide (55.8 g) was added dropwise thereto for 6 hours, while stirring at room temperature. After further stirring at the same temperature for 1 hour, water (1400 mL) was added to the reaction solution, followed by stirring at an inner temperature of 10° C. or lower for 1 hour. The precipitate were collected by filtration, washed with cold water (279 mL) and then dried under a reduced pressure at an outer temperature of 60° C., thereby obtaining white crystals of (2S,4S)-1-[2-[(4-ethoxycarbonylbicyclo[2.2.2]oct-1-yl)amino]acetyl]-4-fluoropyrrolidine-2-carboxamide (obtained amount: 72.9 g, yield: 74%).

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