반응 #1925207

반응 방정식

HCl

HCl

N-(4-Chlorophenyl)-2,2-dimethyl propanamide

TMEDA

n-butyllithium

hexane

ethyl trifluoroacetate

→

title compound

수율 175.0%

4-Chloro-2-trifluoroacetyl-aniline, Hydrochloride Hydrate

수율 175.0%

용매

t-butyl methyl ether

반응 조건

후처리

1. 1
   기타the temperature below 5° C
2. 2
   온도the solution was cooled below −15° C.
3. 3
   workup.WAITAfter 30 min
4. 4
   기타the temperature below 25° C
5. 5
   기타After removal of the aqueous phase
6. 6
   농축the organic solution was concentrated
7. 7
   workup.DISTILLATIONby distilling approximately 200 L of solvent
8. 8
   workup.ADDITIONAcetic acid (352 kg) was added
9. 9
   workup.DISTILLATIONwhile distilling 325 kg solvent under 100 mm vacuum
10. 10
    온도After cooling the solution to 30° C.
11. 11
    온도the mixture heated to 65 to 70° C.
12. 12
    workup.WAITheld 4 hours
13. 13
    온도The resulting slurry was cooled to 5° C.
14. 14
    여과the product was collected by filtration
15. 15
    세척washed with ethyl acetate (50.5 kg)
16. 16
    기타dried in vacuo

실험 절차

N-(4-Chlorophenyl)-2,2-dimethyl propanamide (36.7 kg, 173 mol) was charged to a solution of TMEDA (20.2 kg, 174 mol) in anhydrous t-butyl methyl ether (271.5 kg) and cooled to −20° C. To the cold slurry was added 2.7 N n-butyllithium in hexane (101.9 kg, 393 mol) while keeping the temperature below 5° C. After aging 2 hr at 0 to 5° C., the solution was cooled below −15° C. then rapidly reacted with ethyl trifluoroacetate (34.5 kg, 243 mol). After 30 min, the resulting solution was quenched into 3N HCl (196 L, 589 mol) keeping the temperature below 25° C. After removal of the aqueous phase, the organic solution was concentrated by distilling approximately 200 L of solvent. Acetic acid (352 kg) was added while distilling 325 kg solvent under 100 mm vacuum. After cooling the solution to 30° C., 12 N HCl (43.4 kg, 434 mol) was added and the mixture heated to 65 to 70° C. and held 4 hours. The resulting slurry was cooled to 5° C. and the product was collected by filtration, washed with ethyl acetate (50.5 kg) and dried in vacuo to give 42.1 kg (87%) of the title compound as a white crystalline solid: mp 159-162 dec; 1H NMR (300 MHz, DMSO-d6) d 7.65-7.5 (complex, 2H), 7.1 (d, J=8 Hz, 1H), 7.0 (brs, 3H); 19F NMR (282 MHz, DMSO-d6) δ −69.5.

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