Generalized method:
Step 1: Synthesis of tert-butyl 4-methylene piperidine-1-carboxylate
To a suspension of methyltriphenylphosphonium bromide (36.3 g, 101.6 mmol, 1.35 eq.) in dry ether (300 mL) was added potassium tert-butoxide (1 g, 98 mmol, 1.3 eq.) in a single addition at 0°C under nitrogen protection. The mixture was heated to reflux and stirred for 2 hours. Subsequently, the reaction mixture was cooled to 0 °C using an external ice bath and a solution of N-tert-butoxycarbonyl-4-piperidone (15 g, 75.3 mmol, 1.0 equiv) in ether (60 mL) was added dropwise. The mixture was slowly warmed to room temperature and stirring was continued at this temperature for 1 hour. After that, the mixture was heated to reflux again and stirred overnight (16 hours). Upon completion of the reaction, the mixture was cooled to room temperature, hexane (300 mL) was added, stirred for 10 minutes, filtered, and eluted with a solvent mixture of hexane/EtOAc (100/100 mL). The organic phases were combined and concentrated to give the crude product, which was finally purified by a CombiFlash system (100 g silica gel column, EtOAc/Hexane gradient elution, 0-30%) to give 14 g (94% yield) of tert-butyl 4-methylene piperidine-1-carboxylate as a colorless oil.
1H NMR (400 MHz, CDCl3): δ 4.74 (s, 2H), 3.42 (t, 4H), 2.18 (t, 4H), 1.47 (s, 9H).
