反应详情

To ethyl 1-benzyl-5-fluoro-6-((1-methyl-1H-imidazole-4-sulfonamido)methyl)-2,3-dihydro-1H-inden-2-ylcarbamate (37.5 mg, 0.077 mmol; see example 208) in tetrahydrofuran (1 ml) was added lithium aluminium hydride 1M in tetrahydrofuran (0.231 ml, 0.231 mmol) and the reaction mixture was refluxed for 2 h. Cooled down to room temperature. Added 0.5N potassium hydroxide (1 ml) and water (7 ml), filtered over Celite, washed with tetrahydrofuran and the Celite filter cake was poured into tetrahydrofuran, refluxed for 30 min, and filtered again over Celite. The combined organic layers were evaporated, re-dissolved in dichloromethane, washed with sodium bicarbonate and brine, dried over MgSO4, filtered and evaporated to obtain the crude product as a pale yellow oil that was purified by flash silica gel chromatography on 4 g SiO2-cartridge using 10% methanol in dichloromethane to obtained the desired products cis-N-{[3-benzyl-6-fluoro-2-(methylamino)-2,3-dihydro-1H-inden-5-yl]methyl}-1-methyl-1H-imidazole-4-sulfonamide (7.9 mg, 24%) and trans-N-([3-benzyl-6-fluoro-2-(methylamino)-2,3-dihydro-1H-inden-5-yl]methyl}-1-methyl-1H-imidazole-4-sulfonamide (3.5 mg, 11%)

1. temperaturethe reaction mixture was refluxed for 2 h
2. filtrationfiltered over Celite
3. washwashed with tetrahydrofuran
4. filtrationthe Celite filter cake
5. additionwas poured into tetrahydrofuran
6. temperaturerefluxed for 30 min
7. filtrationfiltered again over Celite
8. customThe combined organic layers were evaporated
9. dissolutionre-dissolved in dichloromethane
10. washwashed with sodium bicarbonate and brine
11. dry with materialdried over MgSO4
12. filtrationfiltered
13. customevaporated
14. customto obtain the crude product as a pale yellow oil that
15. customwas purified by flash silica gel chromatography on 4 g SiO2-cartridge