N-Hydroxyphthalimide → 2-[2-(2,2,2-Trifluoro-ethylamino)-ethoxy]-isoindole-1,3-dione

Participants

Reaction Steps

Diethylazodicarboxylate (3.60 mL, 22.9 mmol) was added dropwise over 30 min to a solution comprised of O-[2-(2,2,2-trifluoro-ethylamino)-ethyl]-hydroxylamine (3.19 g, 22.3 mmol, prepared as in J. Am. Chem. Soc. 1979, 101, 4300), triphenylphosphine (6.05 g, 23.1 mmol), and N-hydroxyphthalimide (3.65 g, 22.4 mmol). The resultant reaction mixture was stirred at ambient temperature. After 20 h, the reaction mixture was concentrated and the residue was dissolved in 60 mL of warm chloroform. Upon cooling, crystallization of diethyl 1,2-hydrazaine dicarboxylate ensued. The precipitate was filtered and the filtrate was concentrated and further diluted with ether. A single crystal of triphenylphosphine oxide was added, initiating copious precipitation. The resultant precipitate was removed by filtration and the filtrate was concentrated in vacuo and chromatographed on silica gel. Elution with hexanes-ethyl acetate (2:1) afforded 2-[2-(2,2,2-trifluoro-ethylamino)-ethoxy]-isoindole-1,3-dione (4.05 g, 63% yield) as a colorless oil: 1H NMR (400 Mz, CDCl3) δ 7.84-7.73 (m, 4H), 4.30 (t, J=4.8 Hz, 2H), 3.26 (q, J=9.5 Hz, 2H), 3.00 (t, J=4.9 Hz, 2H), 2.33 (br s, 1H); MS (APCI+)=289.0.

Provenance & Evidence