反应详情

温度

65 °C

Under a dry nitrogen atmosphere a stirred solution of 2.1 g (0.0062 mole) of N-[2,4-dichloro-5-(1-methylethoxy)anilino]trifluoroacetamidine in 130 mL of toluene was cooled in an ice bath. To this was added 5.2 mL (0.037 mole) of triethylamine followed by the dropwise addition of 45.6 mL of a 2.9% (0.013 mole) phosgene in toluene solution. After complete addition the mixture was heated quickly to 65° C. and stirred at that temperature for 45 minutes. The mixture was allowed to cool to room temperature and stir for approximately 18 hours. The mixture was diluted with 25 mL of water and stirred vigorously for a brief period. Sufficient concentrated hydrochloric acid was added to make the aqueous phase acidic (pH 2). The acidic aqueous phase and the organic phase were shaken briskly after which the organic phase was separated from the mixture and saved for further purification. The aqueous phase was extracted with methylene chloride and the extract evaporated to leave a yellow solid. This solid was dissolved in toluene and the resultant solution added to the saved organic phase from above. The combined organic phase was stirred at room temperature with decolorizing carbon and filtered through a celite pad. The filtrate was extracted with a 1N sodium hydroxide solution. This extract was washed with toluene and acidified with concentrated hydrochloric acid to pH 2. Sodium chloride was added to the acidic solution to the point of saturation. A precipitate formed upon cooling this solution and was collected by filtration. The filter cake was rinsed with several portions of ice cold water and dried under reduced pressure to yield 1.8 g of 1-[2,4-dichloro-5-(1-methylethoxy)phenyl]-3-trifluoromethyl-4,5-dihydro-1,2,4-triazol-5(1H)-one (mp 160°-161° C.), Compound 36.

1. additionAfter complete addition the mixture
2. temperatureto cool to room temperature
3. stirringstir for approximately 18 hours
4. stirringstirred vigorously for a brief period
5. stirringThe acidic aqueous phase and the organic phase were shaken briskly after which the organic phase
6. customwas separated from the mixture
7. customsaved for further purification
8. extractionThe aqueous phase was extracted with methylene chloride
9. customthe extract evaporated
10. customto leave a yellow solid
11. stirringThe combined organic phase was stirred at room temperature with decolorizing carbon
12. filtrationfiltered through a celite pad
13. extractionThe filtrate was extracted with a 1N sodium hydroxide solution
14. washThis extract was washed with toluene
15. additionSodium chloride was added to the acidic solution to the point of saturation
16. customA precipitate formed
17. temperatureupon cooling this solution
18. filtrationwas collected by filtration
19. washThe filter cake was rinsed with several portions of ice cold water
20. customdried under reduced pressure