374794-96-4

General procedure for the synthesis of tert-butyl 2-oxa-8-azaspiro[4.5]decane-8-carboxylate from 4-(2-hydroxyethyl)-4-(hydroxymethyl)-1-piperidinecarboxylic acid 1,1-dimethylethyl ester: A solution of diethyl azodicarboxylate (183 μL, 1.16 mmol) of tetrahydrofuran (0.5 mL) was slowly added dropwise to a stirring 4-(2-hydroxyethyl)-4-(hydroxymethyl)-1-piperidinecarboxylic acid tert-butyl ester (250 mg, 0.96 mmol) at 0 °C. tert-butyl 4-(hydroxyethyl)-4-(hydroxymethyl)-1-piperidinecarboxylate (250 mg, 0.96 mmol) and triphenylphosphine (303 mg, 1.16 mmol) solution in tetrahydrofuran (10 mL) under stirring. The reaction mixture was stirred at 0 °C for 90 min, followed by stirring at room temperature overnight. Afterwards, the mixture was cooled to 0-20 °C and additional triphenylphosphine (126 mg, 0.48 mmol) and diethyl azodicarboxylate (76 μL, 0.48 mmol) were added. The mixture was continued to be stirred at room temperature for 2.5 hours. Upon completion of the reaction, the solvent was removed by evaporation under reduced pressure and the residue was purified by fast column chromatography on silica gel using isohexane/ethyl acetate (80:20) as eluent to afford tert-butyl 2-oxa-8-azaspiro[4.5]decane-8-carboxylate as a colorless oil (150 mg, 65% yield). Mass spectrum (electrospray positive ion mode) m/z: 186 ([M+1-C4H8]+).

[1] Patent: US2003/225059, 2003, A1. Location in patent: Page 27
[2] Patent: US2003/236250, 2003, A1. Location in patent: Page 30
[3] Bioorganic and Medicinal Chemistry Letters, 2002, vol. 12, # 13, p. 1759 - 1762