反应详情

NaH (8.8 mg, 0.22 mmol, 60% w/w in mineral oil) is added to a cooled (0° C.) solution of 2-Methyl-3-{4-[2-(3-methyl-2-oxo-imidazolidin-4-yl)-ethoxy]-phenyl}-2-phenoxy-propionic acid ethyl ester (78.5 mg, 0.18 mmol) in DMF (1 ml). After 5 minutes, the reaction mixture is removed from the cooling bath and stirred while warming to ambient temperature over one hour. After the solution is cooled again to 0° C., 4-(trifluoromethoxy)benzyl bromide (59 ul, 0.37 mmol) is added in a single portion, the cooling bath removed, and the mixture stirred for one hour. The reaction mixture is quenched with 1N HCl and extracted with ethyl acetate (2×). The organic extracts were washed with water, brine, dried (Na2SO4), and concentrated to an oil. The crude product is dissolved in methanol (5 ml), treated with 5N NaOH (0.5 ml), and stirred for 14 hours at ambient temperature. After concentration to remove methanol, the residue is partitioned between diethyl ether and water. The aqueous layer is adjusted to pH 2 with conc. HCl, then extracted with ethyl acetate (2×15 ml). The combined ethyl acetate extracts were washed with water, brine, dried (Na2SO4), and concentrated to an oil which is purified by MS/LC to yield an oil (33 mg, 31%).

1. customthe reaction mixture is removed from the cooling bath
2. temperatureAfter the solution is cooled again to 0° C.
3. customthe cooling bath removed
4. stirringthe mixture stirred for one hour
5. customThe reaction mixture is quenched with 1N HCl
6. extractionextracted with ethyl acetate (2×)
7. washThe organic extracts were washed with water, brine
8. dry with materialdried (Na2SO4)
9. concentrationconcentrated to an oil
10. dissolutionThe crude product is dissolved in methanol (5 ml)
11. additiontreated with 5N NaOH (0.5 ml)
12. stirringstirred for 14 hours at ambient temperature
13. concentrationAfter concentration
14. customto remove methanol
15. customthe residue is partitioned between diethyl ether and water
16. extractionextracted with ethyl acetate (2×15 ml)
17. washThe combined ethyl acetate extracts were washed with water, brine
18. dry with materialdried (Na2SO4)
19. concentrationconcentrated to an oil which
20. customis purified by MS/LC