反应详情

温度

25 °C

2-Amino-5-methanesulfonylamino-benzenesulfonamide (Example 17d, 23.27 g, 87.81 mmol) was dissolved in N,N-dimethylacetamide (100 mL) and diethyl ether (100 mL). Ethyl 3-chloro-3-oxo-propionate (13.88 g, 92.20 mmol) was added and the reaction mixture was stirred at 25° C. for 1 h. The reaction mixture was diluted with ethyl acetate (400 mL) and was extracted with water (400 mL). The aqueous layer was back-extracted with ethyl acetate (2×200 mL). The combined organic layers were dried over sodium sulfate, filtered and most of the solvent was removed in vacuo to a volume of ˜100 mL. To the stirred solution was added hexanes (100 mL) upon which a precipitate formed. The precipitate was collected by vacuum filtration, washed with hexanes and dried under high vacuum to afford the analytically pure product, N-(4-methanesulfonylamino-2-sulfamoyl-phenyl)-malonamic acid ethyl ester (31.22 g, 85.53 mmol, 97.4% yield) as a light-brown solid. 1H NMR (400 MHz, CD3OD) δ: 1.31 (3H, t, J=7.0 Hz), 3.00 (3H, s), 3.59 (2H, s), 4.25 (2H, quartet, J=6.9 Hz), 7.42-7.45 (1H, m), 7.86 (1H, m), 7.92 (1H, d, J=8.8 Hz).

1. extractionwas extracted with water (400 mL)
2. extractionThe aqueous layer was back-extracted with ethyl acetate (2×200 mL)
3. dry with materialThe combined organic layers were dried over sodium sulfate
4. filtrationfiltered and most of the solvent
5. customwas removed in vacuo to a volume of ˜100 mL
6. additionTo the stirred solution was added hexanes (100 mL) upon which a precipitate
7. customformed
8. filtrationThe precipitate was collected by vacuum filtration
9. washwashed with hexanes
10. customdried under high vacuum