Ethyl Acetate → Ethyl 6-(2,3-dichlorobenzyl)-1,4-dihydro-8-fluoro-1-[2-(tert-butyldimethylsilyloxy)ethyl]-4-oxo-3-quinolinecarboxylate

HRID 347887

Reaktionsgleichung

Reaktionsgleichung von HRID 347887
[F:1][C:2]1[CH:3]=[C:4](I)[CH:5]=[C:6]2[C:11]=1[N:10]([CH2:12][CH2:13][O:14][Si:15]([C:18]([CH3:21])([CH3:20])[CH3:19])([CH3:17])[CH3:16])[CH:9]=[C:8]([C:22]([O:24][CH2:25][CH3:26])=[O:23])[C:7]2=[O:27].[Cl-].[Cl:30][C:31]1[C:38]([Cl:39])=[CH:37][CH:36]=[CH:35][C:32]=1[CH2:33][Zn+].[Cl-].[NH4+].C(OCC)(=O)C>C1COCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].O1C=CC=C1P(C1OC=CC=1)C1OC=CC=1.C(Cl)(Cl)Cl>[Cl:30][C:31]1[C:38]([Cl:39])=[CH:37][CH:36]=[CH:35][C:32]=1[CH2:33][C:4]1[CH:5]=[C:6]2[C:11](=[C:2]([F:1])[CH:3]=1)[N:10]([CH2:12][CH2:13][O:14][Si:15]([C:18]([CH3:21])([CH3:20])[CH3:19])([CH3:17])[CH3:16])[CH:9]=[C:8]([C:22]([O:24][CH2:25][CH3:26])=[O:23])[C:7]2=[O:27]

Komponenten

9

Edukt 4

HCID 8857Ethyl AcetateHCID 25517Ammonium ChlorideHCID 23083974Ethyl 1,4-dihydro-8-fluoro-6-iodo-1-[2-(tert-butyldimethylsilyloxy)ethyl]-4-oxo-3-quinolinecarboxylateHCID 178478089HCID 178478089, Verbindung

Produkt 1

HCID 23083923Ethyl 6-(2,3-dichlorobenzyl)-1,4-dihydro-8-fluoro-1-[2-(tert-butyldimethylsilyloxy)ethyl]-4-oxo-3-quinolinecarboxylateAusbeute 101,7 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 521585Tris(furan-2-yl)phosphaneKatalysatorHCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladiumKatalysatorHCID 6212ChloroformLösungsmittelHCID 8028TetrahydrofuranLösungsmittel2×

Versuchsvorschrift

Under an argon stream, 1M solution (2.9 ml, 2.9 mmol) of 2,3-dichlorobenzylzinc chloride in THF obtained in the same manner as in Reference Example 1 was added to THF (20 ml), and then bis(dibenzylideneacetone)palladium(0) (22 mg, 0.039 mmol), tri(2-furyl)phosphine (18 mg, 0.077 mmol) and ethyl 1,4-dihydro-8-fluoro-6-iodo-1-[2-(tert-butyldimethylsilyloxy)ethyl]-4-oxo-3-quinolinecarboxylate (1.0 g, 1.9 mmol) obtained in Step 4 were added. The mixture was stirred at room temperature for 17 hrs, and then a solution (1.0 ml, 1.0 mmol) of 2,3-dichlorobenzylzinc chloride in THF was added. The mixture was heated under reflux for 1 hr. After allowing the mixture to cool, saturated aqueous ammonium chloride solution was added to the reaction solution and insoluble materials were filtered off with Celite. The filtrate was extracted with ethyl acetate, and the organic layer was washed with water and saturated brine, and dried over sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure, and the obtained residue was purified by silica gel chromatography (ethyl acetate:hexane=1:1), and then by PTLC (ethyl acetate:chloroform=1:2) to give an object product (562 mg, yield 53%) as a pale-yellow oil.

Aufarbeitung

  1. temperatureThe mixture was heated
  2. temperatureunder reflux for 1 hr
  3. temperatureto cool
  4. filtrationwere filtered off with Celite
  5. extractionThe filtrate was extracted with ethyl acetate
  6. washthe organic layer was washed with water and saturated brine
  7. dry with materialdried over sodium sulfate
  8. filtrationAfter filtration
  9. concentrationthe filtrate was concentrated under reduced pressure
  10. customthe obtained residue was purified by silica gel chromatography (ethyl acetate:hexane=1:1)

Quellen und Nachweise

ORD-Eintrag
ord-cc984b4f380f4d2db6c4d83cf6727110
Quelldatensatz
uspto-grants-2007_02
Patentnummer
US07176220B2

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