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

HRID 491523Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 491523
[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+]>C1COCC1.O1C=CC=C1P(C1OC=CC=1)C1OC=CC=1>[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

6

Edukt 3

HCID 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 2

HCID 521585Tris(furan-2-yl)phosphaneKatalysatorHCID 8028TetrahydrofuranLösungsmittel2×

Versuchsvorschrift

Under an argon stream, the 1M THF solution (2.9 ml, 2.9 mmol) of 2,3-dichlorobenzylzinc chloride obtained in the same manner as in Reference Example 1 was added to THF (20 ml), then bis(dibenzylidenacetone)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 hr, a solution (1.0 ml, 1.0 mmol) of 2,3-dichlorobenzylzinc chloride in THF was further added, and the mixture was heated under reflux for 1 hr. After allowing to cool, saturated aqueous ammonium chloride solution was added to the reaction mixture, and the insoluble material was filtered through celite. The filtrate was extracted with ethyl acetate. 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 crudely purified by silica gel chromatography (ethyl acetate:hexane=1:1) and successively purified by PTLC (ethyl acetate:chloroform=1:2) to give the 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. filtrationthe insoluble material was filtered through 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 crudely purified by silica gel chromatography (ethyl acetate:hexane=1:1)
  11. customsuccessively purified by PTLC (ethyl acetate:chloroform=1:2)

Quellen und Nachweise

ORD-Eintrag
ord-97b426d439e2420e924e9ee8c1b1d7fa
Quelldatensatz
uspto-grants-2009_05
Patentnummer
US07531554B2

Notizen zur Reaktion

Wird geladen…