反应详情

POCl3 (158.4 μl) was added dropwise to a DMF solution (4 ml) at 0° C. After warming to room temperature, it was stirred for 0.5 hour. Then, a solution of 4-{5-[3-(trifluoromethyl)-4-(2,2,2-trifluoro-1-methylethoxy)phenyl]-1,2,4-oxadiazol-3-yl}-1H-indole (500.0 mg) in DMF (1 ml) was added thereto at 0° C., followed by stirring at room temperature for 15 hours. After cooling to 0° C., to the reaction solution was added a 1M aqueous NaOH solution for adjustment of its pH to 9 to 10. This solution was stirred at 100° C. for 1 hour. After being left to be cooled, to the reaction solution was added water (30 ml), followed by extraction three times with EtOAc (20 ml). The organic layer was combined, washed with saturated brine, dried over anhydrous MgSO4, and then filtered, and the filtrate was concentrated. The residue was purified by silica gel column chromatography (automatic purifier, n-hexane, EtOAc=90:10 to 70:30) to obtain 4-{5-[3-(trifluoromethyl)-4-(2,2,2-trifluoro-1-methylethoxy)phenyl]-1,2,4-oxadiazol-3-yl}-1H-indole-3-carboaldehyde (456.7 mg) as a white solid.

1. customat 0° C.
2. stirringby stirring at room temperature for 15 hours
3. temperatureAfter cooling to 0° C., to the reaction solution
4. stirringThis solution was stirred at 100° C. for 1 hour
5. waitAfter being left
6. temperatureto be cooled, to the reaction solution
7. extractionfollowed by extraction three times with EtOAc (20 ml)
8. washwashed with saturated brine
9. dry with materialdried over anhydrous MgSO4
10. filtrationfiltered
11. concentrationthe filtrate was concentrated
12. customThe residue was purified by silica gel column chromatography (automatic purifier, n-hexane, EtOAc=90:10 to 70:30)