3-Oxo-1-oxa-8-aza-spiro[4.5]decane-8-carboxylic acid tert-butyl ester

240401-09-6

954236-44-3

General procedure for the synthesis of tert-butyl 3-oxo-1-oxa-8-azaspiro[4.5]decane-8-carboxylate from tert-butyl 3-hydroxy-1-oxa-8-azaspiro[4.5]decane-8-carboxylate: tert-butyl 3-hydroxy-1-oxa-8-azaspiro[4.5]decane-8-carboxylate (30 g, 120 mmol) was dissolved at 0 °C in DMSO ( 300 mL) and triethylamine (58.5 mL, 420 mmol) was added. Subsequently, pyridine sulfur trioxide (65 g, 410 mmol, CAS No. 26412-87-3) was added in batches. The reaction mixture was stirred at room temperature for 2 h. The progress of the reaction was monitored by TLC (10% isopropanol/heptane) using iodine stain for color development. Upon completion of the reaction, the solution was poured into ice-cold water (1 L) and extracted with ethyl acetate (3 × 300 mL). The combined organic layers were washed sequentially with 0.5 N HCl (3 × 400 mL), sodium sulfite solution (1 × 400 mL), and saturated brine (1 × 400 mL). The organic layer was dried with anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to give about 33 g of an orange oil. The oily substance was purified by fast column chromatography (2-20% isopropanol/heptane) to afford tert-butyl 3-oxo-1-oxa-8-azaspiro[4.5]decane-8-carboxylate as a white solid (28.8 g, 97% yield). The product was characterized by 1H NMR (400 MHz, CDCl3): δ 1.44-1.52 (m, 9H), 1.61-1.73 (m, 2H), 1.75-1.87 (m, 2H), 2.38 (s, 2H), 3.40 (ddd, J = 13.48, 10.24, 3.24 Hz, 2H), 3.67 (dt, J = 13.57, 4.48 Hz, 2H), 4.04 (s, 2H).