Hydrochloric Acid → 5-{3-[1-(2-Fluoro-5-trifluoromethylphenyl)-cyclopropyl]-2-oxo-propionylamino}-phthalide

HRID 132511

Reaktionsgleichung

Reaktionsgleichung von HRID 132511
S(Cl)(Cl)=O.[F:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]([F:15])([F:14])[F:13])=[CH:8][C:7]=1[C:16]1([CH2:19][C:20](=[O:24])[C:21](O)=[O:22])[CH2:18][CH2:17]1.[NH2:25][C:26]1[CH:27]=[C:28]2[C:33](=[CH:34][CH:35]=1)[C:31](=[O:32])[O:30][CH2:29]2.Cl>CC(N(C)C)=O.C(OCC)(=O)C>[F:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]([F:15])([F:14])[F:13])=[CH:8][C:7]=1[C:16]1([CH2:19][C:20](=[O:24])[C:21]([NH:25][C:26]2[CH:27]=[C:28]3[C:33](=[CH:34][CH:35]=2)[C:31](=[O:32])[O:30][CH2:29]3)=[O:22])[CH2:17][CH2:18]1

Komponenten

7

Edukt 4

HCID 313Hydrochloric AcidHCID 24386Thionyl ChlorideHCID 7206695-Aminophthalide2×HCID 688415163-[1-(2-Fluoro-5-trifluoromethylphenyl)-cyclopropyl]-2-oxo-propionic acid

Produkt 1

HCID 688712075-{3-[1-(2-Fluoro-5-trifluoromethylphenyl)-cyclopropyl]-2-oxo-propionylamino}-phthalide

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 8857Ethyl AcetateLösungsmittelHCID 31374DimethylacetamideLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

At −10° C., 0.84 ml of thionyl chloride are added to 2.9 g of 3-[1-(2-fluoro-5-trifluoromethylphenyl)-cyclopropyl]-2-oxo-propionic acid in 15 ml dimethylacetamide. The mixture is stirred for 30 min. at −10° C. and for 1 hour at 0° C. and then added to 1.95 g of 5-aminophthalide (or, vice versa, 5-aminophthalide may be added to the mixture). After 16 hours at ambient temperature, 2 M hydrochloric acid and ethyl acetate are added, the organic phase is washed to neutral with water, dried over sodium sulfate and concentrated. After chromatography on silica gel (hexane/ethyl acetate: 1+1) and recrystallization from diisopropyl ether, 2.4 g of 5-{3-[1-(2-fluoro-5-trifluoromethylphenyl)-cyclopropyl]-2-oxo-propionylamino}-phthalide (m.p. 168° C.) are obtained.

Aufarbeitung

  1. additionmay be added to the mixture)
  2. waitAfter 16 hours at ambient temperature
  3. washthe organic phase is washed to neutral with water
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated
  6. customAfter chromatography on silica gel (hexane/ethyl acetate: 1+1) and recrystallization from diisopropyl ether, 2.4 g of 5-{3-[1-(2-fluoro-5-trifluoromethylphenyl)-cyclopropyl]-2-oxo-propionylamino}-phthalide (m.p. 168° C.)
  7. customare obtained

Quellen und Nachweise

ORD-Eintrag
ord-0d1bfca890c446e988feafadab5cd626
Quelldatensatz
uspto-grants-2008_06
Patentnummer
US07388006B2

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