反应详情

In a 25 ml single-necked round-bottomed flask, N-Methyl-N-(1-methyl-prop-2-ynyl)-formamide (223 mg) is solubilized in dry dichloromethane (4 ml) at ambient temperature (colourless solution). Under stirring a mixture of phosphorous oxide chloride (0.18 ml) in dichloromethane (1 ml) is added dropwise by syringe. Stirring at ambient temperature is continued for 1 hour. To this solution, 6-(4-Chloro-3-trifluoromethyl-phenoxy)-4-methyl-pyridin-3-ylamine (303 mg) dissolved in 10 ml of dry dichloromethane is added dropwise by syringe, giving a yellow solution. Stirring is continued at an ambient temperature for 3 hours. 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 3:2 (v:v) gives 198 mg of the compound as a brownish oil.

1. additionis added dropwise by syringe
2. stirringStirring at ambient temperature
3. additionis added dropwise by syringe
4. customgiving a yellow solution
5. stirringStirring
6. waitis continued at an ambient temperature for 3 hours
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 3:2 (v:v)