反应详情

In a 25 ml single-necked round-bottomed flask, ethylmethylformamide (350 mg) is solubilized in dry dichloromethane (4 ml) at ambient temperature (colourless solution). Under stirring phosphorous oxide chloride (0.4 ml) is added dropwise by syringe. Stirring at ambient temperature is continued for 1 hour, whereupon a pink-orange solution is obtained. To this solution, 6-(4-Chloro-3-trifluoromethyl-phenoxy)-5-methyl-pyridin-3-ylamine (0.6 g) dissolved in 1.0 ml of dry dichloromethane is added dropwise by syringe, giving a yellow solution. Stirring is continued at an ambient temperature for 1 hour. The mixture is then poured into ice/water (pH=2, water phase). 2 M aqueous NaOH is then added to get a pH of about 11 and stirring is continued for 10 minutes. The mixture is then extracted with dichloromethane (2×50 ml). The combined organic phases are then dried over sodium sulfate, filtered and the solvent is removed in vacuo. Purification of this gum by flash chromatography over silica gel with hexane/ethyl acetate 1:2 (v:v) gives 0.52 g of the compound as a yellow oil.

1. additionUnder stirring phosphorous oxide chloride (0.4 ml) is added dropwise by syringe
2. customis obtained
3. additionis added dropwise by syringe
4. customgiving a yellow solution
5. stirringStirring
6. waitis continued at an ambient temperature for 1 hour
7. customto get a pH of about 11
8. stirringstirring
9. waitis continued for 10 minutes
10. extractionThe mixture is then extracted with dichloromethane (2×50 ml)
11. dry with materialThe combined organic phases are then dried over sodium sulfate
12. filtrationfiltered
13. customthe solvent is removed in vacuo
14. customPurification of this gum by flash chromatography over silica gel with hexane/ethyl acetate 1:2 (v:v)