反应详情

温度

60 °C

A one liter three-neck flask was charged with 4-tert-butylsalicylaldehyde (Step 1) (100.0 g, 0.56 mole), dimethylformamide (110 mL), and potassium carbonate (79.9 g, 0.58 mole) causing the temperature of the mixture to rise to 40° C. Ethyl 4,4,4-trifluorocrotonate (118.0 g, 0.70 mole) in dimethylformamide (110 mL) was added and the mixture heated to 60° C. at which time the reaction temperature rose to 70° C. The reaction was cooled to 60° C., maintained at 60° C. (with added heating) for 8.5 hours and cooled to room temperature. Ethyl acetate (600 mL) and 3 N HCl (600 mL) were added, mixed, and the layers separated. The aqueous phase was extracted with ethyl acetate and the organic phases were combined. The combined organic phases were washed with brine-water (1:1), brine, dried over MgSO4, filtered and concentrated in vacuo, yielding a semi-solid. Hexane (600 mL) was added with mixing and the mixture was filtered. The filtrate was washed with brine, dried over MgSO4, filtered and concentrated in vacua yielding a solid. This solid was dissolved in hot ethanol (600 mL). Water (190 mL) was added which induced crystallization. Filtration of the mixture and drying of the product provided the desired ester as a crystalline solid (131.3 g, 71%): mp 91.0–94.9° C. This material was of suitable purity to be used in subsequent steps without further purification.

1. customto rise to 40° C
2. customrose to 70° C
3. temperatureThe reaction was cooled to 60° C.
4. temperaturemaintained at 60° C.
5. addition(with added heating) for 8.5 hours
6. temperaturecooled to room temperature
7. additionmixed
8. customthe layers separated
9. extractionThe aqueous phase was extracted with ethyl acetate
10. washThe combined organic phases were washed with brine-water (1:1), brine
11. dry with materialdried over MgSO4
12. filtrationfiltered
13. concentrationconcentrated in vacuo
14. customyielding a semi-solid
15. additionwith mixing
16. filtrationthe mixture was filtered
17. washThe filtrate was washed with brine
18. dry with materialdried over MgSO4
19. filtrationfiltered
20. concentrationconcentrated in vacua
21. customyielding a solid
22. customcrystallization
23. filtrationFiltration of the mixture
24. customdrying of the product