Ethyl fluoroacetate → 1-(5-Bromo-2-fluorophenyl)-2-fluoroethanone

Temperatur

-78 °C

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.

1. stirringthe reaction was stirred at −78° C. for 20 minutes
2. stirringstirred at −45° C. for 30 minutes
3. custombefore being quenched with saturated aqueous ammonium chloride at −45° C
4. additionThe mixture was diluted with water and ethyl acetate
5. customThe layers were separated
6. extractionthe aqueous layer was extracted with ethyl acetate
7. washThe combined organic extracts were washed with saturated aqueous ammonium chloride, water, and saturated aqueous sodium chloride
8. dry with materialdried over anhydrous magnesium sulfate
9. filtrationfiltered
10. concentrationconcentrated
11. dissolutionThe crude product was dissolved in a minimal amount of methanol
12. waitplaced in a −20° C. freezer overnight
13. customThe resulting solid was collected
14. washwashed with cold methanol

ORD-Eintrag

ord-90cdd91fd6f140b0ad607f52051758cf

Quelldatensatz

uspto-grants-2016_04

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09309263B2