Hydrochloric Acid → Trifluoroacetic acid

HRID 1255166

Reaktionsgleichung

Reaktionsgleichung von HRID 1255166
[F:1][C:2]([F:46])([F:45])[C:3]1[N:7]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=3[O:20][CH2:21][C:22]3[CH:27]=[CH:26][C:25](/[CH:28]=[CH:29]/[C:30]4[CH:35]=[CH:34][C:33]([C:36]([F:39])([F:38])[F:37])=[CH:32][CH:31]=4)=[CH:24][CH:23]=3)[N:9]=2)[N:6]=[CH:5][C:4]=1[C:40]([O:42]CC)=[O:41].[H][H].[OH-:49].[Li+].Cl.CC[O:54]C(C)=O>O1CCOCC1.[Pt](=O)=O>[C:3]([OH:54])([C:2]([F:46])([F:45])[F:1])=[O:49].[F:46][C:2]([F:1])([F:45])[C:3]1[N:7]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=3[O:20][CH2:21][C:22]3[CH:27]=[CH:26][C:25]([CH2:28][CH2:29][C:30]4[CH:35]=[CH:34][C:33]([C:36]([F:39])([F:37])[F:38])=[CH:32][CH:31]=4)=[CH:24][CH:23]=3)[N:9]=2)[N:6]=[CH:5][C:4]=1[C:40]([OH:42])=[O:41]

Komponenten

9

Edukt 5

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 8857Ethyl AcetateHCID 86633490Ethyl 5-(trifluoromethyl)-1-(6-{2-[(4-{(E)-2-[4-(trifluoromethyl)phenyl]vinyl}benzyl)oxy]phenyl}pyridin-2-yl)-1H-pyrazole-4-carboxylateHCID 178418361HCID 178418361, Verbindung

Produkt 2

HCID 6422Trifluoroacetic acidHCID 252331245-(Trifluoromethyl)-1-(6-{2-[(4-{2-[4-(trifluoromethyl)phenyl]ethyl}benzyl)oxy]phenyl}pyridin-2-yl)-1H-pyrazole-4-carboxylic acid

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 345198Adams' catalystKatalysatorHCID 312751,4-DioxaneLösungsmittel2×

Versuchsvorschrift

To a degassed solution of the title compound from Example 3 Step A (24.0 mg, 0.038 mmol) in EtOAc (2 mL) was added platinum(IV) oxide (8.0 mg). The reaction mixture was fitted with a hydrogen balloon attached to a 3-way adapter. The reaction flask was then evacuated and back-filled with hydrogen. After this process was repeated three times, the reaction mixture was placed under a hydrogen atmosphere and was stirred vigorously. After 45 min, the reaction mixture was filtered through Celite, rinsing with EtOAc. The mixture was concentrated in vacuo and used without further purification: LCMS m/z 640.6 [M+H]+. To a solution of the hydrogenation product in 1,4-dioxane (2 mL) was added lithium hydroxide (1.0 mL, 2.0 M in water, 2.00 mmol), and the resulting mixture was stirred at 50° C. After 30 min, the reaction mixture was rendered acidic by addition of aqueous hydrochloric acid, then was diluted with 1,4-dioxane and passed through a 0.45 micron syringe filter. Purification by reverse phase HPLC (50 to 100% acetonitrile in water, each with 0.1% v/v TFA) provided the title compound: LCMS m/z 612.5 [M+H]+; 1H NMR (500 MHz, d6-DMSO) δ 8.12 (d, J=8.0 Hz, 1H), 8.11 (s, 1H), 8.08 (t, J=8.0 Hz, 1H), 7.74 (dd, J=8.0, 1.5 Hz, 1H), 7.69 (d, J=7.5 Hz, 1H), 7.60 (d, J=8.5 Hz, 2H), 7.43 (d, J=8.5 Hz, 2H), 7.33 (d, J=8.0 Hz, 2H), 7.26 (d, J=8.5 Hz, 2H), 7.22 (d, J=8.0 Hz, 2H), 7.09 (t, J=8.5 Hz, 1H), 5.20 (s, 2H), 2.97-2.94 (m, 2H), 2.91-2.88 (m, 2H).

Aufarbeitung

  1. customattached to a 3-way adapter
  2. customThe reaction flask was then evacuated
  3. additionback-filled with hydrogen
  4. filtrationthe reaction mixture was filtered through Celite
  5. washrinsing with EtOAc
  6. concentrationThe mixture was concentrated in vacuo
  7. customused without further purification
  8. stirringthe resulting mixture was stirred at 50° C
  9. waitAfter 30 min
  10. filtrationfilter
  11. customPurification by reverse phase HPLC (50 to 100% acetonitrile in water

Quellen und Nachweise

ORD-Eintrag
ord-9b8e6117751a4202a559345542b198a3
Quelldatensatz
uspto-grants-2013_06
Patentnummer
US08455638B2

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