N-Hydroxyphthalimide → Propanoic acid,2-[(1,3-dihydro-1,3-dioxo-2H-isoindol-2-yl)oxy]-,1,1-dimethylethyl ester,(2S)-

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Reaction Steps

Prepared according to Yamawaki et al. Bioorg. Med. Chem. 2007, 15, 6716. To a slurry of N-hydroxyphthalimide (517 mg, 3.17 mmol) and potassium carbonate (657 mg, 4.76 mmol) in DMF (4.5 mL) was added (R)-tert-butyl 2-chloropropanoate (522 mg, 3.17 mmol). Additional DMF (4.5 mL) was added after the slurry became viscous. After stirring for 5 d it was diluted with EtOAc and poured into LiCl soln (5% aq, 90 mL). The aqueous layer was extracted with EtOAc (3×) and the combined organic layers were washed with LiCl (5% aq), brine, dried over Na2SO4 and concd in vacuo. The crude residue was purified by silica gel chromatography (EtOAc-Heptane, 0-50%), affording the title compound (348 mg, 38%) as a white solid. LCMS: Rt=0.89 min, m/z=314.0 (M+23) Method 2m_acidic; 1H NMR (400 MHz, CDCl3) δ 7.87-7.81 (m, 2H), 7.75 (dd, J=5.5, 3.1 Hz, 2H), 4.79 (q, J=6.8 Hz, 1H), 1.61 (s, 3H), 1.46 (s, 9H).

Provenance & Evidence