Synthesis
To a flame-dried RB flask with tert-butyl 4-methylenepiperidine-1- carboxylate (2.96 g, 15 mmol, 1.0 equiv) and Zn/Cu couple (6.54 g, 172.5 mmol, 11.5 equiv) under vacuum, t-BuOMe (60 mL) was charged and refilled the flask with N2 balloon. To the mixture thus obtained stirred at 15 °C, a solution of 2,2,2- trichloroacetyl chloride in DME (20 mL) was added dropwise. The mixture was stirred at room temperature overnight after addition. To the reaction mixture stirred in an external ice- bath, a saturated solution of NH4CI (60 mL) was added slowly and carefully (especially the first few drops). After addition, the mixture was stirred at room temperature for 4 h and filtered to remove the solid. The phases were separated. The aqueous phase was extracted with EtOAc. The combined organic phase was washed with brine, dried over anhydrous Na2S04, and concentrated to give the residue, which was purified by CombiFlash (40 g silica gel column, EtOAc/Hexane: 0-40percent) to afford 619 mg (15%) of tert-butyl 2-oxo-7-azaspiro[3.5]nonane-7-carboxylate.
References
[1] Patent: CN106674112, 2017, A. Location in patent: Paragraph 0037-0038
[2] Patent: WO2013/13308, 2013, A1. Location in patent: Paragraph 00199-00201
