1-Oxa-6-azaspiro[2.5]octane-6-carboxylic acid, 1,1-dimethylethyl ester

79099-07-3

147804-30-6

General procedure for the synthesis of tert-butyl 1-oxa-6-azaspiro[2.5]octane-6-carboxylate from N-tert-butoxycarbonyl-4-piperidone: [Reference Example 1] Synthesis of tert-butyl 6-azaspiro[2.5]octane-6-carboxylate. 60% NaH-oil packet (5.28 g, 132 mmol) was suspended in dimethylsulfoxide (DMSO) (250 mL) and after cooling to 0°C, trimethylsulfonium iodide (29.0 g, 132 mmol) was added. The reaction mixture was warmed to room temperature and stirred for 40 min. Subsequently, N-Boc-4-piperidone (Boc = tert-butoxycarbonyl) (25.0 g, 125 mmol) was added and the reaction mixture was stirred at room temperature for 1 hr and then at 55 °C for 1.5 hrs. After completion of the reaction, the mixture was poured into ice-cooled water (500 mL) and extracted with ethyl acetate (AcOEt) (500 mL × 3 times). The ethyl acetate layers were combined, washed with water, then with saturated brine and finally dried with anhydrous Na2SO4. After filtration, the filtrate was concentrated to give tert-butyl 6-aza-1-oxaspiro[2.5]octane-6-carboxylate. The product was structurally confirmed by 1H-NMR. The yield was 26.4 g (99%).1H-NMR (270 MHz, CDCl3): δ 1.40-1.49 (m, 2H), 1.46 (s, 9H), 1.74-1.85 (m, 2H), 2.69 (s, 2H), 3.37-3.48 (m, 2H), 3.68-3.77 (m, 2H).