1,1'-Carbonyldiimidazole → Ethyl 3-(2-fluoro-5-iodophenyl)-3-oxopropanoate

HRID 1070614Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1070614
C(N1C=CN=C1)(N1C=CN=C1)=O.[F:13][C:14]1[CH:22]=[CH:21][C:20]([I:23])=[CH:19][C:15]=1[C:16]([OH:18])=O.C1CCN2C(=NCCC2)CC1.C[Si]([CH:39](C([O-])=O)[C:40]([O:42][CH2:43][CH3:44])=[O:41])(C)C>C1COCC1.C(#N)C>[F:13][C:14]1[CH:22]=[CH:21][C:20]([I:23])=[CH:19][C:15]=1[C:16](=[O:18])[CH2:39][C:40]([O:42][CH2:43][CH3:44])=[O:41]

Komponenten

7

Edukt 4

HCID 682631,1'-CarbonyldiimidazoleHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 27789252-Fluoro-5-iodobenzoic acidHCID 22397230Ethyl trimethylsilylmalonate

Produkt 1

HCID 22397214Ethyl 3-(2-fluoro-5-iodophenyl)-3-oxopropanoateAusbeute 71,4 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6342AcetonitrileLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

Employing the method utilized by Wang (Wang, X., Monte, W. T., Napier, J. J., Ghannam, A. Tetrahedron. Lett. 1994, 35, 9323), 1,1′-carbonyldiimidazole (1.82 g) in THF (20 mL) at 0° C. is treated with 2-fluoro-5-iodobenzoic acid (2.66 g) prepared according to literature procedures (Blackburn, B. K., Lee, A., Baier, M., Kohl, B., Olivero, A. G., Matamoros, R., Robarge, K. D., McDowell, R. S. J. Med Chem. 1997, 40, 717-729.) in portions over a 10 minute period. The mixture is stirred for 1 h and then allowed to warm to room temperature for an additional 1 h. The solution is then added dropwise into an enolate solution of ethyl trimethylsilymalonate at 5° C. prepared by the addition of DBU (3.35 g) to a solution of ethyl trimethylsilylmalonate (2.25 g) in acetonitrile (20 mL) at 5° C. with stirring for 45 minutes. The reaction mixture is allowed to warm to room temperature and stirred overnight. The orange solution is quenched with 100 mL of aqueous 10% citric acid solution and extracted with ethyl acetate. The organic extract is washed with aqueous 10% sodium bicarbonate solution and water, dried (Na2SO4), and concentrated in vacuo to give 2.4 g of the title compound as a yellow liquid. Physical characteristics: tlc Rf=0.66 (silica gel G; 20% EtOAc/hexane, visualize with I2).

Aufarbeitung

  1. customprepared
  2. stirringwith stirring for 45 minutes
  3. temperatureto warm to room temperature
  4. stirringstirred overnight
  5. customThe orange solution is quenched with 100 mL of aqueous 10% citric acid solution
  6. extractionextracted with ethyl acetate
  7. extractionThe organic extract
  8. washis washed with aqueous 10% sodium bicarbonate solution and water
  9. dry with materialdried (Na2SO4)
  10. concentrationconcentrated in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-bf6ededbab804cc58aba9af51ac31615
Quelldatensatz
uspto-grants-2005_06
Patentnummer
US06903097B2

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