Water → 5-Methoxy-3,3-dimethylisoindolin-1-one

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Reaction Steps

To an ice-cold slurry of FeCl3 (35.69 g, 220 mmol) in dry DCE (800 mL) is added a solution of isocyanate 56 (19.12 g, 100.0 mmol) in the same solvent (100 mL) over 45 min. After completion of the addition, GC analysis of an aliquot indicates complete reaction. Water (600 mL) is added and the resulting mixture is stirred vigorously. The layers are separated, and the organic phase is washed 2×1 L with 1 M tartaric acid solution and once with brine. The solution is dried (MgSO4), filtered and evaporated to a dark liquid. This is purified by FC (1:4 hexane/EtOAc, then EtOAc) to provide the 5-methoxy isoindolone 57 as a pale yellow solid, mp 146-147° C., 7.38 g (39%), and the regioisomeric 7-methoxy isoindolone 61 as a yellow solid, mp 155-158° C., 2.85 g (15%). For 57: 1H NMR (CDCl3) 7.74 (d, 1, J=8.5), 7.00-6.95 (m, 1), 6.85 (d, 1, J=2.2), 3.89 (s, 3), 1.54 (s, 6); 13C NMR (CDCl3) 169.57, 163.19, 155.44, 125.31, 123.14, 114.18, 105.92, 58.64, 55.61, 27.81; MS (MW=191.2, EI, eE=70 eV) m/z 191 (M+), 176 (base peak), 161, 133, 118, 88, 77, 63, 42.

Provenance & Evidence