Hydrochloric Acid → (-)-4-(4,4-Difluorocyclohexyl)-3-{fluoro[4-(trifluoromethyl)phenyl]methyl}-7,7-dimethyl-2-(1-{5-[(1E)-3-methylbut-1-ene-1-yl]pyrimidin-2-yl}piperidin-4-yl)-5,6,7,8-tetrahydroquinolin-5-ol

HRID 715873Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 715873
[F:1][C:2]1([F:60])[CH2:7][CH2:6][CH:5]([C:8]2[C:17]3[CH:16]([O:18]CC4C=CC(OC)=CC=4)[CH2:15][C:14]([CH3:29])([CH3:28])[CH2:13][C:12]=3[N:11]=[C:10]([CH:30]3[CH2:35][CH2:34][N:33]([C:36]4[N:41]=[CH:40][C:39]([CH:42](O)[CH2:43][CH:44]([CH3:46])[CH3:45])=[CH:38][N:37]=4)[CH2:32][CH2:31]3)[C:9]=2[CH:48]([F:59])[C:49]2[CH:54]=[CH:53][C:52]([C:55]([F:58])([F:57])[F:56])=[CH:51][CH:50]=2)[CH2:4][CH2:3]1.Cl.C(=O)([O-])O.[Na+]>O1CCOCC1>[F:60][C:2]1([F:1])[CH2:3][CH2:4][CH:5]([C:8]2[C:17]3[CH:16]([OH:18])[CH2:15][C:14]([CH3:28])([CH3:29])[CH2:13][C:12]=3[N:11]=[C:10]([CH:30]3[CH2:31][CH2:32][N:33]([C:36]4[N:41]=[CH:40][C:39](/[CH:42]=[CH:43]/[CH:44]([CH3:45])[CH3:46])=[CH:38][N:37]=4)[CH2:34][CH2:35]3)[C:9]=2[CH:48]([F:59])[C:49]2[CH:50]=[CH:51][C:52]([C:55]([F:56])([F:58])[F:57])=[CH:53][CH:54]=2)[CH2:6][CH2:7]1

Komponenten

5

Edukt 3

HCID 313Hydrochloric AcidHCID 516892Sodium BicarbonateHCID 86682448HCID 86682448, Verbindung

Produkt 1

HCID 86682447(-)-4-(4,4-Difluorocyclohexyl)-3-{fluoro[4-(trifluoromethyl)phenyl]methyl}-7,7-dimethyl-2-(1-{5-[(1E)-3-methylbut-1-ene-1-yl]pyrimidin-2-yl}piperidin-4-yl)-5,6,7,8-tetrahydroquinolin-5-olAusbeute 73 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

To a solution of 118 mg (0.141 mmol) of 4-(4,4-Difluorocyclohexyl)-3-{fluoro[4-(trifluoromethyl)phenyl]methyl}-2-{1-[5-(1-hydroxy-3-methylbutyl)pyrimidin-2-yl]piperidin-4-yl}-5-[(4-methoxybenzyl)oxy]-7,7-dimethyl-5,6,7,8-tetrahydroquinoline, which was prepared by a method similar to that of Reference Example 27, in 2 ml of 1,4-dioxane, 2 ml of 2 N hydrochloric acid was added, and the reaction solution was stirred at 100° C. for 3.5 hours. After completion of the reaction, the reaction solution was poured into saturated sodium hydrogencarbonate aqueous solution and extracted with ethyl acetate. The organic layer was washed with saturated sodium chloride aqueous solution and dried with anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The obtained residue was subjected to silica gel column chromatography [n-hexane/ethyl acetate=92/8-88/12 (V/V)] and the fraction including the desired compound was concentrated under reduced pressure to provide 72 mg of the title compound as a white solid (yield: 73%).

Aufarbeitung

  1. customAfter completion of the reaction
  2. extractionextracted with ethyl acetate
  3. washThe organic layer was washed with saturated sodium chloride aqueous solution
  4. dry with materialdried with anhydrous magnesium sulfate
  5. distillationthe solvent was distilled off under reduced pressure
  6. concentrationwas concentrated under reduced pressure

Quellen und Nachweise

ORD-Eintrag
ord-1ddf966d83ad45279fed2fb6814e6af2
Quelldatensatz
uspto-grants-2015_11
Patentnummer
US09187450B2

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