Phthalimide → (2S,3R)-Benzyl 2-((1,3-dioxoisoindolin-2-yl)methyl)-3-methylpiperidine-1-carboxylate

Participants

Reaction Steps

To a stirred solution of (2S,3R)-benzyl 2-(hydroxymethyl)-3-methylpiperidine-1-carboxylate (4.61 g, 17.5 mmol) and n-Bu3P (10.6 g, 52.4 mmol) in anhydrous THF (150 mL) was added 1,1′-(azodicarbonyl)dipiperidine (ADDP; 8.83 g, 35.0 mmol) at rt under nitrogen. The reaction mixture was stirred at rt for 30 min. To the reaction mixture was then added isoindoline-1,3-dione (3.09 g, 21.0 mmol), followed by heating at reflux for 20 h. After this time, the reaction mixture was cooled to rt, diluted with Et2O (100 mL), and further cooled with an ice/water bath. The resulting mixture was filtered and the filter cake was washed with Et2O (40 mL). The combined filtrate was concentrated under reduced pressure. The resulting residue was purified by flash column chromatography on silica gel eluting with hexanes/CH2Cl2/EtOAc (50:48:2) to hexanes/CH2Cl2/EtOAc (50:42:8). The material obtained from the chromatography was triturated with hexanes/CH2Cl2 (5:1) and solids removed by filtration. Concentration of the filtrate afforded the title compound as a colorless oil (6.12 g, 89%). ESI MS (M+H) 393.

Provenance & Evidence