4-(4-Chloro-3-fluoro-2-methoxyphenyl)-2-hydroxy-2-(trifluoromethyl)pent-4-enal → 4-(4-Chloro-3-fluoro-2-methoxyphenyl)-2-hydroxy-2-(trifluoromethyl)pentanal

HRID 1362485Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1362485
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=[CH2:18])[CH2:9][C:10]([OH:17])([C:13]([F:16])([F:15])[F:14])[CH:11]=[O:12])=[C:4]([O:19][CH3:20])[C:3]=1[F:21].[H][H]>CO.C(O)(=O)C.[Pd]>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([CH3:18])[CH2:9][C:10]([OH:17])([C:13]([F:16])([F:15])[F:14])[CH:11]=[O:12])=[C:4]([O:19][CH3:20])[C:3]=1[F:21]

Komponenten

6

Edukt 2

HCID 866153184-(4-Chloro-3-fluoro-2-methoxyphenyl)-2-hydroxy-2-(trifluoromethyl)pent-4-enalHCID 178418361HCID 178418361, Verbindung

Produkt 1

HCID 866153194-(4-Chloro-3-fluoro-2-methoxyphenyl)-2-hydroxy-2-(trifluoromethyl)pentanal

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 23938PalladiumKatalysatorHCID 176Acetic AcidLösungsmittelHCID 887MethanolLösungsmittel

Versuchsvorschrift

760 mg (2.67 mmol) of 1,1′-bi-2-naphthol are admixed with 2.68 ml (1.34 mmol) of a 0.5 M titanium tetraisopropoxide solution in toluene and the red solution is stirred at room temperature for an hour. 5.07 g (28.1 mmol) of 3-chloro-2-fluoro-6-(1-methyleneethyl)anisole and 3.25 ml (26.7 mmol) of ethyl trifluoropyruvate are added and the mixture is heated at 140° C. for 17 hours. After it has cooled it is immediately purified by column chromatography on silica gel (pentane/diethyl ether 25-40%) to give 1.47 g of ethyl 4-(4-chloro-3-fluoro-2-methoxyphenyl)-2-hydroxy-2-(trifluoromethyl)pent-4-enoate. 1.47 g (3.97 mmol) of ethyl 4-(4-chloro-3-fluoro-2-methoxyphenyl)-2-hydroxy-2-(trifluoromethyl)pent-4-enoate in 40 ml of diethyl ether are cooled to −15° C. and over 10 minutes 300 mg (7.9 mmol) of lithium aluminum hydride in solid form are added in portions. The mixture is stirred for 1 hour, during which it warms to 0° C., and is poured into saturated ammonium chloride solution. Saturated tartaric acid solution is added and the mixture is stirred for 30 minutes. The phases are separated and subjected to repeated extraction with ethyl acetate. The extracts are washed with saturated sodium chloride solution and dried over sodium sulphate and the solvent is removed in vacuo. Separation by column chromatography on silica gel (hexane/ethyl acetate 0-50%) yields 0.38 g of 4-(4-chloro-3-fluoro-2-methoxyphenyl)-2-hydroxy-2-(trifluoromethyl)pent-4-enal and 0.15 g of alcohol. 0.27 g of 4-(4-chloro-3-fluoro-2-methoxyphenyl)-2-hydroxy-2-(trifluoromethyl)-pent-4-enal is dissolved in 14 ml of methanol and 0.3 ml of acetic acid, and 27 mg of palladium on carbon (10%) are added. The suspension is shaken for 2 hours under a hydrogen atmosphere under atmospheric pressure until the hydrogen uptake is 46 ml. The mixture is filtered through Celite, the filter bed being rinsed thoroughly with ethyl acetate. Removal of the solvent gives 027 g of 4-(4-chloro-3-fluoro-2-methoxyphenyl)-2-hydroxy-2-(trifluoromethyl)pentanal as a mixture of the diastereomers.

Aufarbeitung

  1. filtrationThe mixture is filtered through Celite
  2. washthe filter bed being rinsed thoroughly with ethyl acetate
  3. customRemoval of the solvent

Quellen und Nachweise

ORD-Eintrag
ord-8449fb0127ac4df085ad769695dff5e4
Quelldatensatz
uspto-grants-2011_02
Patentnummer
US07880042B2

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