反应详情

温度

-78 °C

2-Formyl-4,5,6,7-tetrahydro-benzoimidazole-1-sulfonic acid dimethylamide was prepared following a modification of the procedure found in the Journal of Medicinal Chemistry, 40; 14, 1997, 2205. To a solution of 4,5,6,7-tetrahydro-benzoimidazole-1-sulfonic acid dimethylamide (2.67 g, 11.6 mmol) in dry THF (100 mL) under argon at −78° C. was added dropwise 2.5 M n-butyllithium in hexanes (7.0 mL, 17.5 mmol). The reaction was stirred at −78° C. for 1 hour, then DMF (1.1 mL, 13.9 mmol) was added dropwise, and the reaction was warmed to room temperature and stirred for 2 hours. Saturated NH4Cl (25 mL) was added, and the reaction mixture was concentrated, and then diluted with CH2Cl2 (500 mL) and distilled water (25 mL). The layers were separated and the aqueous phase was extracted with CH2Cl2 (2×100 mL). The combined organic extracts were washed with brine (1×100 mL), dried (Na2SO4), and concentrated. Purification of the crude material by column chromatography on silica gel (1:1 hexanes-EtOAc) provided 1.53 g (51%) of 2-formyl-4,5,6,7-tetrahydro-benzoimidazole-1-sulfonic acid dimethylamide as a yellow solid. 1H NMR (CDCl3) δ 1.82-1.86 (m, 4H), 2.66-2.68 (m, 2H), 2.86-2.88 (m, 2H), 2.96 (s, 6H), 9.99 (s, 1H).

1. custom2-Formyl-4,5,6,7-tetrahydro-benzoimidazole-1-sulfonic acid dimethylamide was prepared
2. temperaturethe reaction was warmed to room temperature
3. stirringstirred for 2 hours
4. concentrationthe reaction mixture was concentrated
5. additiondiluted with CH2Cl2 (500 mL)
6. distillationdistilled water (25 mL)
7. customThe layers were separated
8. extractionthe aqueous phase was extracted with CH2Cl2 (2×100 mL)
9. washThe combined organic extracts were washed with brine (1×100 mL)
10. dry with materialdried (Na2SO4)
11. concentrationconcentrated
12. customPurification of the crude material by column chromatography on silica gel (1:1 hexanes-EtOAc)