반응 #714817

반응 방정식

LDA

heptane THF ethylbenzene

1-bromo-4-fluorobenzene

ethyl monofluoroacetate

→

title intermediate

수율 28.4%

1-(5-Bromo-2-fluorophenyl)-2-fluoroethanone

수율 28.4%

용매

THF

반응 조건

후처리

1. 1
   workup.STIRRINGthe reaction was stirred at −78° C. for 20 minutes
2. 2
   workup.STIRRINGstirred at −45° C. for 30 minutes
3. 3
   기타before being quenched with saturated aqueous ammonium chloride at −45° C
4. 4
   workup.ADDITIONThe mixture was diluted with water and ethyl acetate
5. 5
   기타The layers were separated
6. 6
   추출the aqueous layer was extracted with ethyl acetate
7. 7
   세척The combined organic extracts were washed with saturated aqueous ammonium chloride, water, and saturated aqueous sodium chloride
8. 8
   건조dried over anhydrous magnesium sulfate
9. 9
   여과filtered
10. 10
    농축concentrated
11. 11
    workup.DISSOLUTIONThe crude product was dissolved in a minimal amount of methanol
12. 12
    workup.WAITplaced in a −20° C. freezer overnight
13. 13
    기타The resulting solid was collected
14. 14
    세척washed with cold methanol

실험 절차

A 2.0 M solution of LDA in heptane/THF/ethylbenzene (100 mL, 200 mmol) was added dropwise via syringe to a solution of 1-bromo-4-fluorobenzene (20 mL, 182 mmol) in THF (600 mL) at −78° C. After stirring for 2.5 hours at −78° C., ethyl monofluoroacetate (18.47 mL, 191 mmol) was added dropwise via syringe, and the reaction was stirred at −78° C. for 20 minutes and then stirred at −45° C. for 30 minutes before being quenched with saturated aqueous ammonium chloride at −45° C. The mixture was diluted with water and ethyl acetate. The layers were separated and the aqueous layer was extracted with ethyl acetate. The combined organic extracts were washed with saturated aqueous ammonium chloride, water, and saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, filtered, and concentrated. The crude product was dissolved in a minimal amount of methanol and placed in a −20° C. freezer overnight. The resulting solid was collected and washed with cold methanol to afford the title intermediate (12.07 g, 51.6 mmol, 28% yield) as a white solid.

출처