Toluene → 4-(2-Chloro-5-methylphenylcarbamoyl)-3-[4-cyclopropyl-5-(3-isobutylcyclobutyl)isoxazol-3-yl]butanoic acid

HRID 1912057Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1912057
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][C:3]=1[NH:9][C:10]([CH2:12][CH:13]([C:22]1[C:26]([CH:27]2[CH2:29][CH2:28]2)=[C:25]([CH:30]2[CH2:33][CH:32]([CH2:34][CH:35]([CH3:37])[CH3:36])[CH2:31]2)[O:24][N:23]=1)[CH2:14][C:15]([O:17]C(C)(C)C)=[O:16])=[O:11].C1(C)C=CC=CC=1.FC(F)(F)C(O)=O.[OH-].[Na+]>O>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][C:3]=1[NH:9][C:10]([CH2:12][CH:13]([C:22]1[C:26]([CH:27]2[CH2:28][CH2:29]2)=[C:25]([CH:30]2[CH2:31][CH:32]([CH2:34][CH:35]([CH3:37])[CH3:36])[CH2:33]2)[O:24][N:23]=1)[CH2:14][C:15]([OH:17])=[O:16])=[O:11]

Komponenten

6

Edukt 4

HCID 1140TolueneHCID 6422Trifluoroacetic acidHCID 14798Sodium HydroxideHCID 71135567tert-Butyl 4-(2-chloro-5-methylphenylcarbamoyl)-3-[4-cyclopropyl-5-(3-isobutylcyclobutyl)isoxazol-3-yl]butanoate

Produkt 1

HCID 711147924-(2-Chloro-5-methylphenylcarbamoyl)-3-[4-cyclopropyl-5-(3-isobutylcyclobutyl)isoxazol-3-yl]butanoic acidAusbeute 92,9 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 962WaterLösungsmittel

Versuchsvorschrift

tert-Butyl 4-(2-Chloro-5-methylphenylcarbamoyl)-3-[4-cyclopropyl-5-(3-isobutylcyclobutyl)isoxazol-3-yl]butanoate (1.09 g) and toluene (3.2 mL) were mixed. To the mixture was added trifluoroacetic acid (3.2 mL) at ice temperature and the mixture was stirred at RT for 30 min. After water (5 mL) was poured into the reaction mixture dropwise at ice temperature, aqueous 4 N sodium hydroxide was added to the mixture dropwise and the mixture was extracted with ethyl acetate. The organic layer was washed with brine and dried over sodium sulfate. The sodium sulfate was filtered off and the filtrate was concentrated in vacuo. The resultant residue was purified by silica gel column chromatography (Eluent: ethyl acetate/hexane=1/5→1/3→1/2→2/1→methanol/chloroform=1/8) to give the title compound (905 mg). The title compound was analyzed using a chiral column. The retention time of the title compound was 6.6 min., and the optical purity thereof was 94.8% ee.

Aufarbeitung

  1. additionwas added to the mixture dropwise
  2. extractionthe mixture was extracted with ethyl acetate
  3. washThe organic layer was washed with brine
  4. dry with materialdried over sodium sulfate
  5. filtrationThe sodium sulfate was filtered off
  6. concentrationthe filtrate was concentrated in vacuo
  7. customThe resultant residue was purified by silica gel column chromatography (Eluent: ethyl acetate/hexane=1/5→1/3→1/2→2/1→methanol/chloroform=1/8)

Quellen und Nachweise

ORD-Eintrag
ord-24c682ea04944c9fb697900288a33625
Quelldatensatz
uspto-grants-2013_12
Patentnummer
US08604069B2

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