反应详情

To a solution of 2-(4,4-dimethyl-2-oxo-1,4-dihydro-2H-benzo[d][1,3]oxazin-6-yl)-pyrrole-1-carboxylic acid tert-butyl ester (2.0 g, 5.8 mmol) in THF (anhydrous, 50 mL) at −78° C. was added chlorosulfone isocyanate (0.66 mL, 6.7 mmol). After 90 min, DMF (9 mL, 116 mmol) was added and the reaction was allowed to warm to room temperature. The reaction mixture was poured into water (50 mL) and extracted with ethyl acetate (2×50 mL). The organic layers were combined, washed with brine (50 mL), dried over magnesium sulfate, filtered and concentrated in vacuo. Purification via flash column chromatography on silica gel (30% ethyl acetate/hexane) gave 2-(4,4-dimethyl-2-oxo-1,4-dihydro-2H-benzo[d][1,3]oxazin-6-yl)-5-cyano-pyrrole-1-carboxylic acid tert-butyl ester (1.1 g, 52%) as a white powder, mp 165-167° C. 1H NMR (d6-DMSO, 300 MHz) δ1.36 (s, 9H), 1.61 (s, 6 H), 6.44 (d, 1 H, J=3.7 Hz), 6.92 (d, 1 H, J=8.2 Hz), 7.27-7.32 (m, 2 H), 7.36 (‘d’, 1 H, J=1.5 Hz), 10.36 (s, 1 H). MS (EI) m/z 367 [M]+.

1. extractionextracted with ethyl acetate (2×50 mL)
2. washwashed with brine (50 mL)
3. dry with materialdried over magnesium sulfate
4. filtrationfiltered
5. concentrationconcentrated in vacuo
6. customPurification via flash column chromatography on silica gel (30% ethyl acetate/hexane)