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

Participants

Reaction Steps

A solution of PPh3 (21.5 g, 82 mmol) in 30 ml of THF was cooled to 0° C. DIAD (16.1 mL, 82 mmol) was then added dropwise and reaction stirred for 20 min. A solution of (2S,3R)-benzyl 2-(hydroxymethyl)-3-methylpiperidine-1-carboxylate (8.7 g, 32.9 mmol) in 15 mL THF was then added dropwise and stirred at 0° C. for 30 min. Phthalimide (6.3 g, 42.7 mmol) was then added and the reaction was warmed to rt overnight. The resulting suspension was concentrated in vacuo, diluted with EtOAc, washed with water and brine, dried (MgSO4), and concentrated. The crude residue was purified by chromatography on silica gel (EtOAc/hexanes) to give the title compound (14.2 g, 110%, DIAD contamination), which was used without further purification. 1H NMR (CDCl3, 400 MHz) δ 7.72-7.71 (m, 1H), 7.62-7.60 (m, 3H), 7.17-7.13 (m, 3H), 7.05-7.04 (m, 1H), 6.98-6.96 (m, 1H), 4.76-4.69 (m, 1H), 4.54-4.39 (m, 1H), 4.03-3.98 (m, 2H), 3.63-3.54 (m, 1H), 3.25-3.07 (m, 1H), 1.91-1.80 (m, 1H), 1.73-1.54 (m, 2H), 1.47-1.25 (m, 2H), 1.07-1.04 (m, 3H). ESI-MS (m/z): 263.93 [M+1]+.

Provenance & Evidence