Hydrochloric Acid → [4-(6-Chloro-5-isopropyl-pyridazin-3-yloxy)-3,5-dimethyl-phenyl]-acetic acid methyl ester

HRID 2199099Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2199099
[CH3:1][O:2][C:3](=[O:14])[CH2:4][C:5]1[CH:10]=[C:9]([CH3:11])[C:8]([OH:12])=[C:7]([CH3:13])[CH:6]=1.[Cl:15][C:16]1[N:17]=[N:18][C:19](Cl)=[CH:20][C:21]=1[CH:22]([CH3:24])[CH3:23].C(=O)([O-])[O-].[K+].[K+].Cl>CS(C)=O.O.[Cu]I>[CH3:1][O:2][C:3](=[O:14])[CH2:4][C:5]1[CH:6]=[C:7]([CH3:13])[C:8]([O:12][C:19]2[N:18]=[N:17][C:16]([Cl:15])=[C:21]([CH:22]([CH3:24])[CH3:23])[CH:20]=2)=[C:9]([CH3:11])[CH:10]=1

Komponenten

8

Edukt 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 140241623,6-Dichloro-4-isopropylpyridazineHCID 20582798(3,5-Dimethyl-4-hydroxy-phenyl)-acetic acid methyl ester

Produkt 1

HCID 59834457[4-(6-Chloro-5-isopropyl-pyridazin-3-yloxy)-3,5-dimethyl-phenyl]-acetic acid methyl esterAusbeute 67,2 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)KatalysatorHCID 679Dimethyl SulfoxideLösungsmittelHCID 962WaterLösungsmittel

Reaktionsbedingungen

Temperatur
90 °C

Versuchsvorschrift

A solution of (3,5-dimethyl-4-hydroxy-phenyl)-acetic acid methyl ester (6a) (12.5 g, 0.064 mol) in anhydrous dimethyl sulfoxide (256 mL) under argon at room temperature was treated with 3,6-dichloro-4-isopropyl pyridazine (7) (18.43 g, 0.096 mol) followed by anhydrous potassium carbonate (17.69 g, 0.12 mol) and copper (I) iodide (6.09 g, 0.032 mol). The reaction mixture was heated to 90° C. for 24 h. At this time, the reaction was cooled to room temperature and was poured onto a 1N aqueous hydrochloric acid solution (200 mL) and ice. The aqueous layer was diluted with water (100 mL) and extracted with ethyl acetate (2×500 mL). The aqueous layer was made basic (pH=8) by the addition of a 1N aqueous sodium hydroxide solution. The water layer was extracted again with ethyl acetate (1×500 mL). The combined organics were washed with a saturated aqueous sodium chloride solution, dried with magnesium sulfate, filtered and concentrated under vacuum. The resulting residue was purified by column chromatography using silica gel eluted with 5-15% ethyl acetate in petroleum ether to afford [4-(6-chloro-5-isopropyl-pyridazin-3-yloxy)-3,5-dimethyl-phenyl]-acetic acid methyl ester (8a) (15 g, 67%) and a minor amount of isomer as a white solid; EI(+)-HRMS m/z calcd for C18H21ClN2O3 (M+) 348.1241, found 348.1237. Molecular Weight=348.8327; Exact Mass=348.1241

Aufarbeitung

  1. temperatureAt this time, the reaction was cooled to room temperature
  2. extractionextracted with ethyl acetate (2×500 mL)
  3. additionby the addition of a 1N aqueous sodium hydroxide solution
  4. extractionThe water layer was extracted again with ethyl acetate (1×500 mL)
  5. washThe combined organics were washed with a saturated aqueous sodium chloride solution
  6. dry with materialdried with magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under vacuum
  9. customThe resulting residue was purified by column chromatography
  10. washeluted with 5-15% ethyl acetate in petroleum ether

Quellen und Nachweise

ORD-Eintrag
ord-4530955f6b084e0b889cb0c25c9d896e
Quelldatensatz
uspto-grants-2016_06
Patentnummer
USRE046024E1

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