反应详情

温度

-78 °C

To a cold (−78° C.) solution of 2-(thien-2-ylmethyl)-1H-isoindole-1,3(2H)-dione (6.78 g, 27.87 mmol) in DCM (56 mL) was added dropwise (in about 10 min) chlorosulfonic acid (16.237 g, 139.3 mmol, 9.33 mL, d: 1.74) diluted in DCM (9.3 mL). The reaction mixture was stirred 2 h at −78° C., then 1 h at −40° C. and overnight at rt. The resulting brown solution was poured on ice. The mixture was extracted with DCM (3×200 mL), and the combined organic layers were washed with water (3×200 mL), dried over MgSO4, filtered and concentrated to afford a yellowish oil. This crude product was purified by column chromatography over silica gel (AcOEt/c-Hex 1/4 to 1/3 to 1/2 in about 1 h) to give the title compound as a white solid (6.42 g, 67%). 1H NMR (CDCl3, 300 MHz) δ 7.89 (d, 1H. J=5.5 Hz), 7.87 (d, 1H. J=5.5 Hz), 7.76 (d, 1H, J=5.5 Hz), 7.75 (d, 1H, J=5.5 Hz), 7.71 (d, 1H, J=4.0 Hz), 7.18 (d, 1H, J=4.0 Hz), 5.05 (s, 2H). HPLC (Condition A), Rt: 4.6 min (HPLC purity: 94.8%).

1. custom1 h
2. customat −40° C.
3. customovernight
4. customat rt
5. additionThe resulting brown solution was poured on ice
6. extractionThe mixture was extracted with DCM (3×200 mL)
7. washthe combined organic layers were washed with water (3×200 mL)
8. dry with materialdried over MgSO4
9. filtrationfiltered
10. concentrationconcentrated
11. customto afford a yellowish oil
12. customThis crude product was purified by column chromatography over silica gel (AcOEt/c-Hex 1/4 to 1/3 to 1/2 in about 1 h)