Methyl iodide → (2-Chloro-6-trifluoromethyl-pyridin-3-yl)-methyl-amine

To a mixture of N-(2-chloro-6-trifluoromethylpyridin-3-yl)-2,2-dimethylpropionamide (6.59 g) and THF (30 ml), sodium hydride (60% in oily, 1 g) was added under ice-cooling, and stirred at room temperature for 30 minutes. The reaction mixture was ice-cooled, and then methyl iodide (10 g) was added, and stirred at room temperature for 4 hours. Into the reaction mixture, water was poured, and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, and concentrated under reduced pressure. To the resulting residue, acetonitrile (40 ml), concentrated hydrochloric acid (40 ml), and isopropanol (40 ml) were added, and stirred at room temperature for 2 hours, at 60° C. for 2 hours, then at 80° C. for 2 hours. Into the reaction mixture cooled to room temperature, saturated aqueous sodium hydrogen carbonate solution was poured, and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, and concentrated under reduced pressure. The resulting residue was subjected to silica gel column chromatography to give 2.60 g of (2-chloro-6-trifluoromethylpyridin-3-yl)-methylamine.

1. additionwas added under ice-
2. temperaturecooling
3. temperaturecooled
4. stirringstirred at room temperature for 4 hours
5. extractionextracted with ethyl acetate
6. dry with materialThe organic layer was dried over sodium sulfate
7. concentrationconcentrated under reduced pressure
8. additionTo the resulting residue, acetonitrile (40 ml), concentrated hydrochloric acid (40 ml), and isopropanol (40 ml) were added
9. stirringstirred at room temperature for 2 hours, at 60° C. for 2 hours
10. waitat 80° C. for 2 hours
11. temperatureInto the reaction mixture cooled to room temperature
12. additionsaturated aqueous sodium hydrogen carbonate solution was poured
13. extractionextracted with ethyl acetate
14. dry with materialThe organic layer was dried over sodium sulfate
15. concentrationconcentrated under reduced pressure

ORD record

ord-060c07f99c4048e4988e606e5e3696c4

Source dataset

uspto-grants-2016_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09278983B2