反应详情

2-[2-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}phenoxy]propionic acid is dissolved in tetrahydrofuran, to this is added thionyl chloride while stirring, then, the mixture is heated while stirring under reflux condition. Then, the solution is allowed to cool, concentrated, then, dissolved in tetrahydrofuran (hereinafter, referred to as Solution A). Tetrahydrofuran is added to 1-pentyl alcohol, and Solution A is added to this, then, pyridine is added. The mixture is stirred at room temperature, then, 2% aqueous hydrochloric acid is poured into the reaction solution, and extracted with ethyl acetate. The organic layer is washed with saturated saline, and dried over magnesium sulfate, then, concentrated. The residue is subjected to silica gel column chromatography (eluent: hexane/ethyl acetate=5/1) to obtain pentyl 2-[2-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}phenoxy]propionate [compound 3-189 of the present invention].

1. temperaturethe mixture is heated
2. stirringwhile stirring
3. temperatureunder reflux condition
4. temperatureto cool
5. concentrationconcentrated
6. dissolutiondissolved in tetrahydrofuran (hereinafter,
7. additionTetrahydrofuran is added to 1-pentyl alcohol, and Solution A
8. additionis added to this, then, pyridine
9. additionis added
10. stirringThe mixture is stirred at room temperature
11. addition2% aqueous hydrochloric acid is poured into the reaction solution
12. extractionextracted with ethyl acetate
13. washThe organic layer is washed with saturated saline
14. dry with materialdried over magnesium sulfate
15. concentrationconcentrated