Cesium carbonate → 4-[1-(4-Trifluoromethyl-phenyl)-piperidin-4-yl]-butyric acid methyl ester

HRID 511171Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 511171
C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+].Cl.[CH3:54][O:55][C:56](=[O:66])[CH2:57][CH2:58][CH2:59][CH:60]1[CH2:65][CH2:64][NH:63][CH2:62][CH2:61]1.Br[C:68]1[CH:73]=[CH:72][C:71]([C:74]([F:77])([F:76])[F:75])=[CH:70][CH:69]=1>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:54][O:55][C:56](=[O:66])[CH2:57][CH2:58][CH2:59][CH:60]1[CH2:65][CH2:64][N:63]([C:68]2[CH:73]=[CH:72][C:71]([C:74]([F:77])([F:76])[F:75])=[CH:70][CH:69]=2)[CH2:62][CH2:61]1

Komponenten

7

Edukt 4

HCID 10796Cesium carbonateHCID 67872Benzene, 1-bromo-4-(trifluoromethyl)-HCID 634876Binap, (A+-)-HCID 66672062Methyl 4-(piperidin-4-yl)butanoate hydrochloride

Produkt 1

HCID 585764494-[1-(4-Trifluoromethyl-phenyl)-piperidin-4-yl]-butyric acid methyl esterAusbeute 64,7 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 167845palladium(II) acetateKatalysatorHCID 312751,4-DioxaneLösungsmittel

Versuchsvorschrift

A mixture of palladium (II) acetate (42 mg; 0.185 mmol), (±)-2,2′-bis-diphenylphosphanyl-[1,1′]binaphthalenyl (170 mg; 0.275 mmol), cesium carbonate (867 g; 2.66 mmol) in dioxane (5 mL) is placed in an ultrasonic bath for 30 minutes. 4-Piperidin-4-yl-butyric acid methyl ester hydrochloride (290 mg; 1.33 mmol, prepared in accordance with Example 131) and 1-bromo-4-trifluoromethyl-benzene (299 mg; 1.33 mmol) are then added and the reaction mixture is stirred for 2 hours under reflux. After dilution with ethyl acetate, the mixture is filtered and the filtrate concentrated under high vacuum. The obtained residue is purified by column chromatography on silica gel (hexanes/dichloromethane 50:50 v/v to 100) to afford the desired compound (284 mg; 0.86 mmol).

Aufarbeitung

  1. temperatureunder reflux
  2. filtrationAfter dilution with ethyl acetate, the mixture is filtered
  3. concentrationthe filtrate concentrated under high vacuum
  4. customThe obtained residue is purified by column chromatography on silica gel (hexanes/dichloromethane 50:50 v/v to 100)

Quellen und Nachweise

ORD-Eintrag
ord-a3fa80e85c514e58933896c8e38f084c
Quelldatensatz
uspto-grants-2015_08
Patentnummer
US09096524B2

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