Реакция #343936

Уравнение реакции

1-fluoro-2-methyl-4-(3,3,5,5-tetramethyl-1-cyclohexen-1-yl)benzene

formic acid

1,3,5-trioxane

→

2-(4-Fluoro-3-methylphenyl)-4,4,6,6-tetramethylcyclohex-1-enecarboxaldehyde

Растворители

heptane

Условия реакции

Обработка

1. 1
   workup.ADDITIONwas added
2. 2
   Температураthe bath was heated
3. 3
   Температураto reflux for about 3 hours
4. 4
   Другоеto separate
5. 5
   ПромывкаThe top layer was washed with water
6. 6
   workup.ADDITION48 kg of methanol and 7.2 kg of 50% aqueous sodium hydroxide were added
7. 7
   workup.STIRRINGThe mixture was stirred for about 10 minutes
8. 8
   Промывкаwashed with water
9. 9
   Сушкаdried with 10 kg of anhydrous sodium sulfate
10. 10
    ФильтрацияThe sodium sulfate was filtered off
11. 11
    Промывкаthe filter cake was washed with 10 kg of heptane
12. 12
    workup.ADDITIONTo the combined filtrates, 96 kg of dimethyl sulfoxide and 28 kg of triethylamine were added
13. 13
    workup.ADDITIONSulfur trioxide/pyridine complex (36 kg) was then charged portionwise at 30°-35° C
14. 14
    workup.STIRRINGThe batch was agitated for 15 minutes
15. 15
    Другоеthe reaction was quenched with 96 kg of iced water
16. 16
    Другоеto separate
17. 17
    ПромывкаThe top layer was washed with dilute hydrochloric acid and with brine
18. 18
    workup.ADDITIONMethanol (48 kg) and 50% sodium hydroxide (4.8 kg) were added
19. 19
    workup.STIRRINGthe batch was stirred at 21°-25° C. for one hour
20. 20
    workup.ADDITIONIce (0.6 kg) was added
21. 21
    workup.STIRRINGthe mixture was stirred for 15 minutes
22. 22
    Другоеto separate
23. 23
    ПромывкаThe top solution was washed with brine
24. 24
    Концентрированиеconcentrated in vacuo
25. 25
    Другоеto remove the volatiles
26. 26
    workup.DISSOLUTIONThe residue was dissolved in 22 kg of isopropanol
27. 27
    ТемператураThe mixture was then cooled to about -10° C.
28. 28
    workup.STIRRINGstirred for 16 hours
29. 29
    ФильтрацияThe crystallized product was filtered off
30. 30
    Промывкаwashed with cold aqueous isopropanol
31. 31
    Другоеdried to constant weight

Методика

To a mixture of 20 kg of 1-fluoro-2-methyl-4-(3,3,5,5-tetramethyl-1-cyclohexen-1-yl)benzene, 72 kg of 96% formic acid and 3.6 kg of 1,3,5-trioxane, 96 g of 70% benzoyl peroxide catalyst was added and the bath was heated to reflux for about 3 hours. The mixture was then cooled to room temperature and 48 kg of heptane was added with stirring. The phases were allowed to separate and the bottom layer was discarded. The top layer was washed with water, then 48 kg of methanol and 7.2 kg of 50% aqueous sodium hydroxide were added. The mixture was stirred for about 10 minutes, washed with water and dried with 10 kg of anhydrous sodium sulfate. The sodium sulfate was filtered off and the filter cake was washed with 10 kg of heptane. To the combined filtrates, 96 kg of dimethyl sulfoxide and 28 kg of triethylamine were added. Sulfur trioxide/pyridine complex (36 kg) was then charged portionwise at 30°-35° C. The batch was agitated for 15 minutes and the reaction was quenched with 96 kg of iced water. The phases were allowed to separate and the bottom layer was discarded. The top layer was washed with dilute hydrochloric acid and with brine. Methanol (48 kg) and 50% sodium hydroxide (4.8 kg) were added and the batch was stirred at 21°-25° C. for one hour. Ice (0.6 kg) was added and the mixture was stirred for 15 minutes. The phases were allowed to separate and the bottom layer was discarded. The top solution was washed with brine and concentrated in vacuo to remove the volatiles. The residue was dissolved in 22 kg of isopropanol and 2.8 kg of water. The mixture was then cooled to about -10° C., seeded and stirred for 16 hours. The crystallized product was filtered off, washed with cold aqueous isopropanol and dried to constant weight. Yield: 8.5 kg of 2-(4-fluoro-3-methylphenyl)- 4,4,6,6-tetramethylcyclohex-1-enecarboxaldehyde; m.p. 50.5°-51.5° C.

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