反应详情

To a mixture of 54 mg of 2-Methyl-3-{4-[2-(3-methyl-2-oxo-imidazolidin-4-yl)-ethoxy]-phenyl}-2-phenoxy-propionic acid ethyl ester in 2 mL of dry DMF at 0° C. under an atmosphere of nitrogen, 10 mg of NaH (0.253 mmol) is added. The resulting solution is allowed to stand at ambient temperature for 20 min. Then 61 mg of 4-trifluoromethylbenzyl bromide is added and resulting mixture is allowed to stand at ambient temperature for overnight. Reaction mixture is diluted with Et2O and 1N HCl. Organic layer is then washed with 1N HCl (2×10 mL), brine (2×10 mL), dried over Na2SO4, filtered and concentrated under vacuum. The crude material is in 5 mL of EtOH and 0.3 mL of 5N NaOH. The mixture is heated to reflux for 1 h. The organic solvent is then removed under vacuum and residue is dissolved in CH2Cl2 and 1N HCl. Aqueous layer is washed with CH2Cl2 (2×10 mL). Combined organic layer is dried over Na2SO4, filtered and concentrated under vacuum. The crude material is purified by MS/LC to give 35 mg (49%) of the title product. 1H NMR (400 MHz, CDCl3): δ 7.56 (d, 2H, J=8.0 Hz), 7.35 (d, 2H, J=8.0 Hz), 7.28-7.18 (m, 4H), 7.05 (t, 1H, J=7.2 Hz), 6.91 (d, 2H, J=8.0 Hz), 6.74 (d, 2H, J=8.0 Hz), 5.49 (bs, 1H), 4.45, 4.39 (ABq, 2H, J=15.4 Hz), 3.98 (t, 2H, J=5.8 Hz), 3.77-3.65 (m, 1H), 3.42 (t, 1H, J=8.5 Hz), 3.28, 3.14 (ABq, 2H, J=14.0 Hz), 3.05 (t, 1H, J=8.5 Hz), 2.86 (s, 3H), 2.28-2.20 (m, 1H), 1.95-1.85 (m, 1H), 1.43 (s, 3H). HRMS (ES+) m/z exact mass calcd for C30H32N2O5F3 (m+1) 557.2263, found 557.2257.

1. customresulting mixture
2. waitto stand at ambient temperature for overnight
3. customReaction mixture
4. washOrganic layer is then washed with 1N HCl (2×10 mL), brine (2×10 mL)
5. dry with materialdried over Na2SO4
6. filtrationfiltered
7. concentrationconcentrated under vacuum
8. temperatureThe mixture is heated
9. temperatureto reflux for 1 h
10. customThe organic solvent is then removed under vacuum and residue
11. dissolutionis dissolved in CH2Cl2
12. washAqueous layer is washed with CH2Cl2 (2×10 mL)
13. dry with materialCombined organic layer is dried over Na2SO4
14. filtrationfiltered
15. concentrationconcentrated under vacuum
16. customThe crude material is purified by MS/LC