反应详情

Under an atmosphere of argon, 300 mg (0.65 mmol) of methyl 4-({[2,6-dichloro-3-(5-chloro-2-thienyl)phenyl]acetyl}amino)-1,3-thiazole-5-carboxylate were dissolved in 15 ml of tetrahydrofuran, and 23 mg (0.97 mmol) of sodium hydride were added at room temperature. The reaction mixture was stirred at RT for 5 min, and a solution of 167 mg (0.78 mmol) of 2,2-difluoroethyl trifluoromethanesulfonate in 6 ml of THF was then added over a period of 10 min. The mixture is then stirred at RT for 12 h. The THF is removed under reduced pressure and the residue is taken up in water. The aqueous phase is extracted with dichloromethane and the organic phase is dried and concentrated by evaporation. The residue is chromatographed (acetonitrile/water (0.05% trifluoroacetic acid 20/80 to 100/0)). This gave 120 mg of methyl 4-[{[2,6-dichloro-3-(5-chloro-2-thienyl)phenyl]acetyl}(2,2-difluoroethyl)amino]-1,3-thiazole-5-carboxylate.

1. stirringThe mixture is then stirred at RT for 12 h
2. customThe THF is removed under reduced pressure
3. extractionThe aqueous phase is extracted with dichloromethane
4. customthe organic phase is dried
5. concentrationconcentrated by evaporation
6. customThe residue is chromatographed (acetonitrile/water (0.05% trifluoroacetic acid 20/80 to 100/0))