Dimethylformamide → 4-Trifluoromethyl-benzoic acid 1-ethoxycarbonyl-3-methyl-2-oxo-butyl ester

HRID 490722

Reaktionsgleichung

Reaktionsgleichung von HRID 490722
[H-].[Na+].CN(C)C=O.[F:8][C:9]([F:20])([F:19])[C:10]1[CH:18]=[CH:17][C:13]([C:14]([OH:16])=[O:15])=[CH:12][CH:11]=1.[CH2:21]([O:23][C:24](=[O:32])[CH:25](Cl)[C:26](=[O:30])[CH:27]([CH3:29])[CH3:28])[CH3:22]>O>[CH2:21]([O:23][C:24]([CH:25]([O:15][C:14](=[O:16])[C:13]1[CH:17]=[CH:18][C:10]([C:9]([F:19])([F:20])[F:8])=[CH:11][CH:12]=1)[C:26](=[O:30])[CH:27]([CH3:29])[CH3:28])=[O:32])[CH3:22]

Komponenten

6

Edukt 4

HCID 6228DimethylformamideHCID 99664-(Trifluoromethyl)benzoic acidHCID 24758Sodium hydrideHCID 9877606Ethyl 2-chloro-4-methyl-3-oxopentanoate

Produkt 1

HCID 690607214-Trifluoromethyl-benzoic acid 1-ethoxycarbonyl-3-methyl-2-oxo-butyl ester

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 962WaterLösungsmittel

Reaktionsbedingungen

Temperatur
90 °C

Versuchsvorschrift

Sodium Hydride, 60% mineral oil (1.9 g, 46.3 mmol) and dimethylformamide (50 mL) are stirred at room temperature and 4-(trifluoromethyl)benzoic acid (8.0 g, 42.1 mmol) is added. To the resulting slurry is added 2-chloro-4-methyl-3-oxo-pentanoic acid ethyl ester (8.5 g, 44.2 mmol) and the resulting mixture is heated to 90° C. for 3 hr. The reaction mixture is cooled, diluted with water (100 mL), and product is extracted with ethyl acetate (100 mL). The organic layer is washed with water (three 100 mL portions) and brine (100 mL), dried over anhydrous magnesium sulfate, filtered, and concentrated to constant weight to give 4-trifluoromethyl-benzoic acid 1-ethoxycarbonyl-3-methyl-2-oxo-butyl ester as a colorless oil, 14.6 g, 100%. The resulting oil is stirred in a mixture of acetic acid (100 mL) and ammonium acetate (9.75 g, 126.5 mmol) at reflux 1 hr, then 20 hr at room temperature. The solvent is removed in vacuo and the residue is partitioned between aqueous saturated sodium hydrogen carbonate (100 mL) and ethyl acetate (100 mL. The layers are separated, the aqueous layer is washed with ethyl acetate (100 mL). The organic extracts are combined, washed with water and brine (100 mL each) dried over anhydrous magnesium sulfate, filtered, and concentrated. The residue is purified over silica eluting with 9:1 hexanes:ethyl acetate to afford 4-Isopropyl-2-(4-trifluoromethyl-phenyl)-oxazole-5-carboxylic acid ethyl ester as a white solid, 8.1 g, 60%. MS (M++1) 328.

Aufarbeitung

  1. temperatureThe reaction mixture is cooled
  2. extractionis extracted with ethyl acetate (100 mL)
  3. washThe organic layer is washed with water (three 100 mL portions) and brine (100 mL)
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated to constant weight

Quellen und Nachweise

ORD-Eintrag
ord-2dd133c0591b4b009840ccbe855187b1
Quelldatensatz
uspto-grants-2009_05
Patentnummer
US07528160B2

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