Ammonium Chloride → N-[2-(3,5-dibromopyridine-2-yl)-2-oxoethyl]-2-(trifluoromethyl)benzamide

Temperatur

-20 °C

To 5.5 g of 3,5-dibromopyridine in 1 ml of tetrahydrofuran, 22.7 ml of a 1.0M tetrahydrofuran-toluene solution of 2,2,6,6-tetramethylpiperidinylmagnesium 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, 3.0 g of the N-[2-methoxy(methyl)amino-2-oxoethyl]-2-(trifluoromethyl)benzamide prepared in Step 1 in Synthetic Example 17 in 17 ml of tetrahydrofuran was added dropwise, and after the addition, the mixture was stirred at the same temperature for another 1 hour. After completion of the reaction, the reaction mixture was mixed with 30 ml of saturated aqueous ammonium chloride and 20 ml of water and extracted with ethyl acetate (50 ml×2), the resulting organic layers were combined, washed with water (50 ml×1) and dried over saturated aqueous sodium chloride and then anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The resulting 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 659 mg of the desired product as a pale yellow oil.

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 the same temperature for another 1 hour
5. customAfter completion of the reaction
6. extractionextracted with ethyl acetate (50 ml×2)
7. washwashed with water (50 ml×1)
8. dry with materialdried over saturated aqueous sodium chloride
9. customanhydrous sodium sulfate, and the solvent was evaporated under reduced pressure
10. customThe resulting residue was purified by silica gel column chromatography

ORD-Eintrag

ord-7a084dc2967e48f9a2e64d58421cc3cf

Quelldatensatz

uspto-grants-2016_09

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09434684B2