反应详情

To a stirred solution of 2-(3-cyano-benzyl)-1,1-dioxo-1λ6-isothiazolidine-3-carboxylic acid (6.0 g, 21.4 mmol) in tetrahydrofuran (40 mL) was added 1-hydroxybenzotriazole (available from 3B Scientific Corporation, Libertyville, Ill. 60048, USA; 2.8 g, 20.72 mmol), TBTU (6.8 g, 21.18 mmol) and diisopropylethylamine (8.3 g, 64.21 mmol) simultaneously at room temperature. After 16 h of stirring at the same temperature, tetrahydrofuran was distilled off under reduced pressure. The obtained crude residue was extracted with ethyl acetate (120 mL), washed with an aqueous solution of 1N NaOH (50 mL), brine (50 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure to give a crude mass. The crude mass was purified by silica gel column chromatography (100-200 mesh) using a gradient of 50-70% ethyl acetate/hexanes to give 2-(3-cyano-benzyl)-1,1-dioxo-1λ6-isothiazolidine-3-carboxylic acid((1S,2S,3S,5R)-2,6,6-trimethyl-bicyclo[3.1.1]hept-3-yl)-amide (7.0 g, 79.5%).

1. distillationwas distilled off under reduced pressure
2. customThe obtained crude residue
3. extractionwas extracted with ethyl acetate (120 mL)
4. washwashed with an aqueous solution of 1N NaOH (50 mL), brine (50 mL)
5. dry with materialdried over anhydrous sodium sulfate
6. concentrationconcentrated under reduced pressure
7. customto give a crude mass
8. customThe crude mass was purified by silica gel column chromatography (100-200 mesh)