Reaction #2358541

Reaction equation

trifluoroacetic acid

K2CO3

K2CO3

DPPA

3-cyclohexene-1(R)-carboxylic acid

→

N-(Cyclohex-3-en-1(R)-yl)-2,2,2-trifluoro-acetamide

Solvents

chlorobenzene

triethylamine

chlorobenzene

chlorobenzene

Conditions

Workup

1. 1
   Otherthe mixture obtained
2. 2
   workup.ADDITIONwas added dropwise
3. 3
   OtherThe mixture obtained
4. 4
   Temperaturemaintaining the temperature at 80 to 90° C.
5. 5
   Washsteady gas evolution and a 20 ml of chlorobenzene line rinse
6. 6
   OtherThe mixture obtained
7. 7
   workup.STIRRINGwas stirred at 78 to 82° C. for 1 h
8. 8
   OtherThe mixture obtained
9. 9
   Temperaturewas cooled to approximately 70° C.
10. 10
    Temperaturemaintaining the temperature at 70 to 80° C.
11. 11
    Washa 25 ml chlorobenzene line rinse
12. 12
    OtherThe mixture obtained
13. 13
    workup.STIRRINGwas stirred at 90 to 95° C. for 2 h
14. 14
    OtherThe mixture obtained
15. 15
    Temperaturewas cooled to 15 to 25° C.
16. 16
    Otherthe mixture obtained
17. 17
    workup.STIRRINGwas stirred for 15 min
18. 18
    OtherThe layers obtained
19. 19
    Otherwere separated and to the upper organic layer
20. 20
    Otherobtained
21. 21
    OtherThe mixture obtained
22. 22
    Filtrationwas filtered through celite
23. 23
    Otherto remove residual solid
24. 24
    Washthe celite was washed with 50 ml of chlorobenzene
25. 25
    OtherThe layers obtained
26. 26
    Otherwere separated
27. 27
    Otherobtained
28. 28
    Extractionwere back extracted with 250 ml of chlorobenzene
29. 29
    Otherthe combined organic phases obtained
30. 30
    Washwere washed with 500 ml of 0.5 M phosphoric acid
31. 31
    OtherThe aqueous layer obtained
32. 32
    Extractionwas back extracted with 300 ml of chlorobenzene
33. 33
    Otherthe combined organic phases obtained
34. 34
    Washwere washed with 500 ml of 5% aqueous NaCl solution

Procedure

50 g of 3-cyclohexene-1(R)-carboxylic acid and 425 ml of chlorobenzene were charged to a flask at 20-25° C. and the mixture obtained was stirred. To the mixture obtained 110 ml of triethylamine was added dropwise followed by 25 ml of chlorobenzene. The mixture obtained was warmed to 78 to 82° C. and 109.2 g of DPPA was added in a dose controlled fashion, maintaining the temperature at 80 to 90° C. and steady gas evolution and a 20 ml of chlorobenzene line rinse was given. The mixture obtained was stirred at 78 to 82° C. for 1 h until complete determined by TLC. The mixture obtained was cooled to approximately 70° C. and 226 g of trifluoroacetic acid in 34 ml of chlorobenzene was added dropwise maintaining the temperature at 70 to 80° C., followed by 1.57 g of CuCl and a 25 ml chlorobenzene line rinse. The mixture obtained was stirred at 90 to 95° C. for 2 h and the reaction was followed by TLC until completion. The mixture obtained was cooled to 15 to 25° C. and 375 ml of 20% aqueous K2CO3 solution added and the mixture obtained was stirred for 15 min. The layers obtained were separated and to the upper organic layer obtained was added 375 ml of 20% aqueous K2CO3 solution. The mixture obtained was filtered through celite to remove residual solid and the celite was washed with 50 ml of chlorobenzene. The layers obtained were separated. The combined lower aqueous layers obtained were back extracted with 250 ml of chlorobenzene and the combined organic phases obtained were washed with 500 ml of 0.5 M phosphoric acid. The aqueous layer obtained was back extracted with 300 ml of chlorobenzene and the combined organic phases obtained were washed with 500 ml of 5% aqueous NaCl solution.

Source