反应详情

温度

0 °C

A slurry of 2-hydroxy-3-(4-{2-[1-(4-methoxy-benzyl)-3-methyl-2-oxo-imidazolidin-4-yl]-ethoxy}-phenyl)-2-methyl-propionic acid ethyl ester (7.35 g, 15.62 mmol) and sodium hydride (2.5 g, 62.5 mmol, 60% dispersion on mineral oil) in DMF (50 mL) i stirred for 45 minutes, then cooled to 0° C. Iodobutane (36 mL, 312 mmol, d=1.617) and 18-crown-6 16.5 g, 62.5 mmol) are added, then the reaction mixture is stirred 18 h at ambient temperature and diluted with ethyl acetate. The organic layer is washed, then dried concentrated in vacuo, and diluted with ethanol (400 mL) and 5N NaOH (40 mL). The reaction mixture is refluxed for 1 h, cooled to ambient temperature, and concentrated in vacuo. The residue is washed, dried, concentrated, and re-dissolved in ethanol (300 mL). Concentrated H2SO4 (30 mL) is added to the reaction solution, then the mixture is refluxed 1 h, cooled to ambient temperature, concentrated, and diluted with ethyl acetate. The organic layer is washed, dried, and concentrated to provide the title compound (5.3 g, 65%). 1H NMR (400 MHz, CDCl3): δ 7.17 (d, 2H, J=8.8 Hz), 7.09 (d, 2H, J=8.8 Hz), 6.84 (d, 2H, J=8.8 Hz), 6.70 (d, 2H, J=8.8 Hz), 4.32, 4.28 (ABq, 2H, J=14.7 Hz), 4.17-4.11 (m, 2H), 3.93 (t, 2H, J=5.9 Hz), 3.78 (s, 3H), 3.61-3.53 (m, 3H), 3.40-3.31 (m, 3H), 2.97-2.89 (m, 3H), 2.97-2.89 (m, 3H), 2.81 (s, 3H), 2.25-2.15 (m, 1H), 1.89-1.81 (m, 1H), 1.59-1.49 (m, 2H), 1.42-1.33 (m, 2H), 1.29 (s, 3H), 1.24 (t, 3H, J=7.2 Hz), 0.91 (t, 3H, J=7.2 Hz). Rf=0.43 in 50% acetone in hexanes.

1. washThe organic layer is washed
2. customdried
3. concentrationconcentrated in vacuo
4. additiondiluted with ethanol (400 mL) and 5N NaOH (40 mL)
5. temperatureThe reaction mixture is refluxed for 1 h
6. temperaturecooled to ambient temperature
7. concentrationconcentrated in vacuo
8. washThe residue is washed
9. customdried
10. concentrationconcentrated
11. dissolutionre-dissolved in ethanol (300 mL)
12. additionConcentrated H2SO4 (30 mL) is added to the reaction solution
13. temperaturethe mixture is refluxed 1 h
14. temperaturecooled to ambient temperature
15. concentrationconcentrated
16. additiondiluted with ethyl acetate
17. washThe organic layer is washed
18. customdried
19. concentrationconcentrated