反应详情

To 3-(2-fluorophenyl)-4-hydroxy-5-methyl-5H-furan-2-one (18.7 g, 90 mmol) in ethanol (90 ml) was added hydrazine hydrate (24 ml, 0.45 mol), and the mixture was stirred at reflux for 3 days. The solution was concentrated to approximately 30 ml, and was then stirred at 90° C. for 1 week. Hydrazine hydrate (24 ml, 0.45 mol) was added, and the mixture was stirred at 90° C. for another week. More hydrazine hydrate (24 ml, 0.45 mol) was added, and the solution was stirred as before for 1 week, and was then allowed to concentrate to approximately 30 mL Ethanol (90 ml) and hydrazine hydrate (24 ml, 0.45 mol) were added, and the mixture was heated at reflux for 1 week. The solvent was removed in vacuo, yielding a glassy foam. This was suspended in dichloromethane (200 ml) and tosyl chloride (20.4 g, 0.107 mol) and triethylamine (16.3 ml, 0.165 mol) were added at 5° C. The solution was allowed to warm to room temperature and was stirred overnight. The mixture was washed with saturated sodium chloride solution (1×100 ml), dried over magnesium sulfate, and was then concentrated in vacuo. The residue was purified by flash chromatography on silica gel (20 to 50% ethyl acetate in dichloromethane, UV detection), yielding toluene-4-sulfonic acid 4-(2-fluorophenyl)-5-(1-hydroxyethyl)-1H-pyrazol-3-yl ester as a yellow glass, which solidified upon standing (17.6 g). 1H NMR (400 MHz, CDCl3) δ 1.33 (3H, d, J=6.6 Hz), 2.38 (3H, s), 5.01 (1H, q, J=6.6 Hz), 6.98 (1H, m), 7.11 (3H, m), 7.27 (2H, m), 7.80 (2H, d, J=8.3 Hz), 10.30 (1H, br s); MS (ES+) m/e 377 [MH]+.

1. temperatureat reflux for 3 days
2. concentrationThe solution was concentrated to approximately 30 ml
3. stirringwas then stirred at 90° C. for 1 week
4. stirringthe mixture was stirred at 90° C. for another week
5. stirringthe solution was stirred as before for 1 week
6. additionwere added
7. temperaturethe mixture was heated
8. temperatureat reflux for 1 week
9. customThe solvent was removed in vacuo
10. customyielding a glassy foam
11. stirringwas stirred overnight
12. washThe mixture was washed with saturated sodium chloride solution (1×100 ml)
13. dry with materialdried over magnesium sulfate
14. concentrationwas then concentrated in vacuo
15. customThe residue was purified by flash chromatography on silica gel (20 to 50% ethyl acetate in dichloromethane, UV detection)