Methyl acetoacetate → Methyl 5-amino-3-oxo-5-(2-fluoro-5-methoxyphenyl)-pent-4-enoate

HRID 2380397Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2380397
[C:1]([O:7][CH3:8])(=[O:6])[CH2:2][C:3]([CH3:5])=[O:4].[H-].[Na+].C([Li])CCC.[F:16][C:17]1[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][C:18]=1[C:19]#[N:20]>C1COCC1>[NH2:20][C:19]([C:18]1[CH:21]=[C:22]([O:25][CH3:26])[CH:23]=[CH:24][C:17]=1[F:16])=[CH:5][C:3](=[O:4])[CH2:2][C:1]([O:7][CH3:8])=[O:6]

Komponenten

6

Edukt 4

HCID 7757Methyl acetoacetateHCID 24758Sodium hydrideHCID 27745462-Fluoro-5-methoxybenzonitrileHCID 178418339Butyllithium

Produkt 1

HCID 70062292Methyl 5-amino-3-oxo-5-(2-fluoro-5-methoxyphenyl)-pent-4-enoate

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

Following the procedure of Huckin and Wilson (Can. J. Chem. 1974, p 1346), 850 mg of methyl acetoacetate (7.32 mmol, 1 eq.) were added slowly to a cooled (0° C.) and stirring suspension of NaH (60% dispersion in mineral oil, 1 eq.) in dry THF. When evolution of H2 had ceased (10 min.), 1.05 equivalents of n-butyllithium (2.5M in hexanes) were slowly added, producing an orange solution. After an additional 10 minutes at 0° C., 1 equivalent of 2-fluoro-5-methoxybenzonitrile (1.11 grams, 7.32 mmol) was added dropwise and the resulting red solution was allowed to come to room temperature. After stirring overnight (20 h) the reaction mixture was brought to 0° C. and quenched with 1.5 mL of 12M HCl followed by H2O (20 mL). The mixture was extracted with ether (4×) and the combined ether layers were washed (4×) with saturated aqueous NaCl solution, dried (Na2SO4) and concentrated to give a red oil. Purification via column chromatography (Silica gel, EtOAc/Hexanes eluent) afforded methyl 5-amino-3-oxo-5-(2-fluoro-5-methoxyphenyl)-pent-4-enoate as a pale yellow oil.

Aufarbeitung

  1. additionwere added slowly to
  2. additionwere slowly added
  3. customproducing an orange solution
  4. customto come to room temperature
  5. stirringAfter stirring overnight (20 h) the reaction mixture
  6. customwas brought to 0° C.
  7. customquenched with 1.5 mL of 12M HCl
  8. extractionThe mixture was extracted with ether (4×)
  9. washthe combined ether layers were washed (4×) with saturated aqueous NaCl solution
  10. dry with materialdried (Na2SO4)
  11. concentrationconcentrated
  12. customto give a red oil
  13. customPurification via column chromatography (Silica gel, EtOAc/Hexanes eluent)

Quellen und Nachweise

ORD-Eintrag
ord-8466d84e1bd14d74842bb0c611f43c47
Quelldatensatz
uspto-grants-1994_11
Patentnummer
US05367077

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