反应详情

温度

60 °C

To a solution of cis-2-{(3,3-dimethylbutyl)-[2-(7-methanesulfonylamino-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-3-yl)acetyl]amino}-cyclopentanecarboxylic acid ethyl ester (125.8 mg, 0.226 mmol) in absolute ethanol (10 mL) was added a 21% w/w solution of sodium ethoxide in ethanol (0.84 mL, 2.25 mmol). After stirring at 60° C. for 4 h, the mixture was diluted with ethyl acetate and acidified with 1.0 M aqueous hydrochloric acid solution to pH 1. The organic layer was separated and the aqueous layer was extracted with ethyl acetate (2×20 mL). The combined organic layers were dried over anhydrous magnesium sulfate and concentrated in vacuo. The crude mixture was purified by flash column chromatography (Teledyne Isco RediSep Flash Column; 0-100% ethyl acetate in hexanes) to afford the desired product, cis-N-{3-[2-(3,3-dimethylbutyl)-5-hydroxy-3-oxo-2-aza-bicyclo[4.3.0]non-4-en-4-yl]-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-7-yl}-methanesulfonamide (52.7 mg, 0.103 mmol, 46%), as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ 0.94 (9H, s), 1.56-1.57 (5H, m), 2.08-2.15 (3H, m), 3.05 (3H, s), 3.17 (1H, bs), 3.34 (1H, bs), 3.64-3.72 (1H, m), 3.90 (1H, bs), 7.48-7.60 (3H, m), 10.17 (1H, bs). LC-MS (ESI) calcd for C22H30N4O6S2 510.16, found 511.4 [M+H+]. Anal. calcd for C22H30N4O6S2 0.3H2O: C, 51.20; H, 5.98; N, 10.86; S, 12.43, found C, 51.39; H, 5.81; N, 10.65; S, 12.26.

1. customThe organic layer was separated
2. extractionthe aqueous layer was extracted with ethyl acetate (2×20 mL)
3. dry with materialThe combined organic layers were dried over anhydrous magnesium sulfate
4. concentrationconcentrated in vacuo
5. customThe crude mixture was purified by flash column chromatography (Teledyne Isco RediSep Flash Column; 0-100% ethyl acetate in hexanes)