Water → N-[2-(3,5-dichloropyridin-2-yl)-2-oxoethyl]-2-(trifluoromethyl)benzamide

Temperature

-20 °C

To 17.6 g of 2-bromo-3,5-dichloropyridin in 5 ml of tetrahydrofuran, 58.3 ml of a 1.3M tetrahydrofuran solution of isopropylmagnesium chloride-lithium chloride complex was added dropwise with stirring at −20° C., and after the addition, the mixture was stirred at the same temperature for 30 minutes. Then, to the reaction mixture, 10.0 g of N-[2-methoxy(methyl)amino-2-oxoethyl]-2-(trifluoromethyl)benzamide in 57.4 ml of tetrahydrofuran was added dropwise, and after the addition, the mixture was stirred at room temperature for another 3 hours. After completion of the reaction, the reaction mixture was mixed with 100 ml of saturated aqueous ammonium chloride and 100 ml of water and extracted with ethyl acetate (150 ml×2), the resulting organic layers were combined, washed with water (100 ml×1) and dried over saturated aqueous sodium chloride and then anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography using ethyl acetate-hexane (with a gradient of from 5:95 to 50:50) as the eluent to obtain 3.0 g of the desired product as pale yellow crystals.

1. additionafter the addition
2. stirringthe mixture was stirred at the same temperature for 30 minutes
3. additionafter the addition
4. stirringthe mixture was stirred at room temperature for another 3 hours
5. customAfter completion of the reaction
6. extractionextracted with ethyl acetate (150 ml×2)
7. washwashed with water (100 ml×1)
8. dry with materialdried over saturated aqueous sodium chloride
9. distillationanhydrous sodium sulfate, and the solvent was distilled off under reduced pressure
10. customThe residue was purified by silica gel column chromatography

ORD record

ord-bc768c29b3d24c4e8bdb266ca2fdaeab

Source dataset

uspto-grants-2016_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09434684B2