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

HRID 632613Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 632613
[F:1][C:2]1([F:55])[CH2:7][CH2:6][CH:5]([C:8]2[C:17]3[C@@H: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]([OH:42])=[CH:38][N:37]=4)[CH2:32][CH2:31]3)[C:9]=2[C@@H:43]([F:54])[C:44]2[CH:49]=[CH:48][C:47]([C:50]([F:53])([F:52])[F:51])=[CH:46][CH:45]=2)[CH2:4][CH2:3]1.Cl.C(=O)([O-])O.[Na+]>O1CCOCC1>[F:55][C:2]1([F:1])[CH2:3][CH2:4][CH:5]([C:8]2[C:17]3[C@@H: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]([OH:42])=[CH:38][N:37]=4)[CH2:34][CH2:35]3)[C:9]=2[C@@H:43]([F:54])[C:44]2[CH:45]=[CH:46][C:47]([C:50]([F:51])([F:53])[F:52])=[CH:48][CH:49]=2)[CH2:6][CH2:7]1

Komponenten

5

Edukt 3

HCID 313Hydrochloric AcidHCID 516892Sodium BicarbonateHCID 89683078HCID 89683078, Verbindung

Produkt 1

HCID 56598385(5S)-4-(4,4-Difluorocyclohexyl)-3-{(S)-fluoro[4-(trifluoromethyl)phenyl]methyl}-2-[1-(5-hydroxypyrimidin-2-yl)piperidin-4-yl]-7,7-dimethyl-5,6,7,8-tetrahydroquinolin-5-olAusbeute 94,2 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

To a solution of 453 mg (0.589 mmol) of 2-[4-((5S)-4-(4,4-Difluorocyclohexyl)-3-{(S)-fluoro[4-(trifluoromethyl)phenyl]methyl}-5-[(4-methoxybenzyl)oxy]-7,7-dimethyl-5,6,7,8-tetrahydroquinolin-2-yl)piperidin-1-yl]pyrimidin-5-ol, which was prepared by a method similar to that of Reference Example 14, in 5 ml of 1,4-dioxane, 1 ml of 6 N hydrochloric acid was added, and the mixture was stirred at 80° C. for 4.5 hours. After completion of the reaction, the reaction solution was poured into saturated sodium hydrogencarbonate aqueous solution and extracted with ethyl acetate. The obtained organic phases were combined and washed with saturated sodium chloride aqueous solution, and then the solvent was distilled off under reduced pressure. The obtained residue was subjected to silica gel column chromatography [n-hexane/ethyl acetate=76/24-40/60 (V/V)] and the fraction including the desired compound was concentrated under reduced pressure to provide 360 mg of the title compound as a white solid (yield: 94%).

Aufarbeitung

  1. customAfter completion of the reaction
  2. extractionextracted with ethyl acetate
  3. washwashed with saturated sodium chloride aqueous solution
  4. distillationthe solvent was distilled off under reduced pressure
  5. concentrationwas concentrated under reduced pressure

Quellen und Nachweise

ORD-Eintrag
ord-f7e505f990ca46489412e78af573a34d
Quelldatensatz
uspto-grants-2016_04
Patentnummer
US09321747B2

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