1-Piperidinepropanoic acid, 3-(ethoxycarbonyl)-, ethyl ester → 1-Azabicyclo(3.3.1)nonan-4-one

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A suspension of potassium tert-butoxide (12.03 g, 107 mmol; Aldrich) in toluene (200 mL) was heated to reflux for 15 minutes, then a solution of ethyl 1-(3-ethoxy-3-oxopropyl)piperidine-3-carboxylate (10.70 g, 41.6 mmol; Example 35A) in toluene (50 mL) was added dropwise over 2 hour to the refluxing reaction mixture. After the addition was complete, the reaction was heated to reflux for an additional 2 hours, cooled to ambient temperature, and extracted with water (3×50 mL). The combined aqueous layers were acidified with concentrated hydrochloric acid (40 mL), then heated to reflux for 22 hours. The reaction was basified with 45 weight % potassium hydroxide (˜35 mL) and extracted with chloroform (3×100 mL). The combined organic extracts were dried over sodium sulfate, filtered and concentrated in vacuo to afford the title compound: 1H NMR (300 MHz, CDCl3) δ ppm 1.50-1.81 (m, 2 H), 1.90-1.96 (m, 2 H), 2.39-2.43 (m, 1 H), 2.49-2.54 (m, 2 H), 3.08-3.41 (m, 6 H); MS (DCI/NH3) m/z 140 (M+H)+.

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