Water → (2S)-2-[4-(t-butoxycarbonylamino-methyl)-1,3-dioxo-1,3-dihydro-isoindol-2-yl]-4-carbamoyl-butyric acid t-butyl ester

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Reaction Steps

Triethylamine (1.2 g, 11.8 mmol) was added to a stirred suspension of (1,3-dioxo-1,3-dihydro-isobenzofuran-4-ylmethyl)carbamic acid t-butyl ester (2.1 g, 7.9 mmol) and L-glutamine t-butyl ester hydrochloride (2.1 g, 8.6 mmol) in toluene (90 mL). The mixture was refluxed under Dean-Stark water separator overnight. The mixture was cooled to room temperature and diluted with CH2Cl2 (60 mL). The solution was washed with H2O (2×40 mL) and brine (40 mL), and dried (MgSO4). Solvent was removed, and the residue was purified by chromatography (silica gel) to give (2S)-2-[4-(t-butoxycarbonylamino-methyl)-1,3-dioxo-1,3-dihydro-isoindol-2-yl]-4-carbamoyl-butyric acid t-butylester (1.1 g, 29%): 1H NMR (CDCl3) δ 1.41 (s, 9H), 1.43 (s, 9H), 2.25-3.60 (m, 4H), 4.65 (d, J=6.5 Hz, 2H), 4.76-4.82 (dd, J=4.9 and 9.8 Hz, 1H), 5.47-5.61 (m, 3H), 7.67-7.79 (m, 3H); Chiral HPLC: Daicel ChiralPak AD, 46×250 mm, 20/80 IPA/hexane, 1 mL/min, 240 nm, 8.87 min (98% ee).

Provenance & Evidence