반응 #91086

반응 방정식

TMEDA

HCl

bromo-2-(trifluoromethyl)benzene

bromocyclopentane

magnesium

magnesium

→

title compound

1-Cyclopentyl-2-(trifluoromethyl)benzene

용매

—

heptanes

THF

THF

THF

THF

MTBE

반응 조건

후처리

1. 1
   기타To a 50 L three-neck round-bottom flask equipped with a mechanical stirrer
2. 2
   기타resulting in a clear greenish solution
3. 3
   온도cooled to 0-5° C
4. 4
   온도to maintain the internal temperature below 10° C
5. 5
   온도to maintain the internal temperature below 20° C
6. 6
   기타The resulting reaction mixture
7. 7
   온도was heated to 40-45° C. for 1 hour
8. 8
   workup.ADDITIONwas added to the reaction mixture at a rate
9. 9
   온도to maintain an internal temperature below 25° C
10. 10
    기타The resulting reaction mixture
11. 11
    workup.STIRRINGto stir at room temperature overnight
12. 12
    온도subsequently cooled to an internal temperature of 0-5° C
13. 13
    온도to maintain the internal temperature below 15° C. (caution, very exothermic)
14. 14
    workup.STIRRINGthe reactor contents was stirred for 30 min
15. 15
    기타The phases were separated
16. 16
    추출the aqueous layer back extracted with MTBE (75 L)
17. 17
    세척The combined organic layers were washed with H2O (50 L), brine (50 L)
18. 18
    건조dried (MgSO4)
19. 19
    여과The mixture was filtered through an in-line (1 micron)
20. 20
    여과filter cartridge
21. 21
    여과filter cartridge into a clean dry reactor
22. 22
    기타The solvent was evaporated under vacuum (jacket ≦30° C.)
23. 23
    기타to provide a viscous liquid
24. 24
    세척The silica plug was eluted with heptanes (TLC, Rf˜0.8, silica gel, heptanes)
25. 25
    workup.ADDITIONthe fractions containing the product
26. 26
    기타were evaporated

실험 절차

To a 50 L three-neck round-bottom flask equipped with a mechanical stirrer, thermocouple, and nitrogen inlet, was added dry THF (35 L) and cooled to 0-5° C. To the flask was added Iron (III) chloride (2.7 kg, 0.15 eq) portion wise over 30-60 min. and stirred for 15-30 min. resulting in a clear greenish solution. Under a nitrogen atmosphere in a dry 100 gallon glass lined reactor was added THF (87.5 L) and magnesium turnings (4.05 kg, 1.5 eq), and cooled to 0-5° C. To the THF and magnesium mixture was added the solution of FeCl3 in THF at a rate to maintain the internal temperature below 10° C. To the resulting yellow/green mixture was added TMEDA (15.5 kg, 1.2 eq) at a rate to maintain the internal temperature below 20° C. The resulting reaction mixture was heated to 40-45° C. for 1 hour and a mixture of 1 bromo-2-(trifluoromethyl)benzene (25 kg, 1.0 eq) and bromocyclopentane (19.9 kg, 1.2 eq) was added to the reaction mixture at a rate to maintain an internal temperature below 25° C. The resulting reaction mixture was allowed to stir at room temperature overnight and subsequently cooled to an internal temperature of 0-5° C. To the resulting mixture was added 6 N HCl (100 L, 1.5 h) at such a rate as to maintain the internal temperature below 15° C. (caution, very exothermic). After the quench, MTBE (200 L) was added and the reactor contents was stirred for 30 min. The phases were separated and the aqueous layer back extracted with MTBE (75 L). The combined organic layers were washed with H2O (50 L), brine (50 L) and dried (MgSO4). The mixture was filtered through an in-line (1 micron) filter cartridge followed by an additional in-line (0.45 micron) filter cartridge into a clean dry reactor. The solvent was evaporated under vacuum (jacket ≦30° C.) and co-evaporated with heptanes (2×25 L) to provide a viscous liquid. The viscous liquid was dissolved in heptanes (100 L) and passed through a silica plug (25 kg). The silica plug was eluted with heptanes (TLC, Rf˜0.8, silica gel, heptanes) and the fractions containing the product were evaporated to provide the title compound as a yellow liquid, 11.7 kg (49.2%), purity as determined by HPLC was 94.1%. 1H NMR conforms to reference standard.

출처