Hydrochloric Acid → (-)-4-(4,4-Difluorocyclohexyl)-3-{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 715847Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 715847
[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](N5CCOCC5)=[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-])[OH:63].[Na+].[OH-].[Na+]>O1CCOCC1.CO>[F:1][C:2]1([F:60])[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[CH2:35][CH2:34][N:33]([C:36]4[N:41]=[CH:40][C:39]([OH:63])=[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)[CH2:6][CH2:7]1

Komponenten

7

Edukt 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 516892Sodium BicarbonateHCID 866824274-(4,4-Difluorocyclohexyl)-3-{fluoro[4-(trifluoromethyl)phenyl]methyl}-5-[(4-methoxybenzyl)oxy]-7,7-dimethyl-2-{1-[5-(morpholin-4-yl)pyrimidin-2-yl]piperidin-4-yl}-5,6,7,8-tetrahydroquinoline

Produkt 1

HCID 76372263(-)-4-(4,4-Difluorocyclohexyl)-3-{fluoro[4-(trifluoromethyl)phenyl]methyl}-2-[1-(5-hydroxypyrimidin-2-yl)piperidin-4-yl]-7,7-dimethyl-5,6,7,8-tetrahydroquinolin-5-olAusbeute 78 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 887MethanolLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
70 °C

Versuchsvorschrift

To 4.30 g (5.13 mmol) of (−)-4-(4,4-Difluorocyclohexyl)-3-{fluoro[4-(trifluoromethyl)phenyl]methyl}-5-[(4-methoxybenzyl)oxy]-7,7-dimethyl-2-{1-[5-(morpholin-4-yl)pyrimidin-2-yl]piperidin-4-yl}-5,6,7,8-tetrahydroquinoline, which was prepared by a method similar to that of Reference Example 12, 14 ml of conc. hydrochloric acid, 36 ml of methanol and 40 ml of 1,4-dioxane were added, and the reaction solution was stirred at 70° C. for 1.5 hours. After completion of the reaction, the reaction solution was poured into 200 ml of saturated sodium hydrogencarbonate aqueous solution to which 14 ml of 6 N sodium hydroxide aqueous solution had been added 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=3/1-2/1 (V/V)] and the fraction including the desired compound was concentrated under reduced pressure. Toluene was added to the obtained residue and the precipitate was obtained by filtration to provide 2.60 g of the title compound as a white solid (yield: 78%).

Aufarbeitung

  1. additionwere added
  2. customAfter completion of the reaction
  3. additionhad been added
  4. extractionextracted with ethyl acetate
  5. washThe organic layer was washed with saturated sodium chloride aqueous solution
  6. dry with materialdried with anhydrous magnesium sulfate
  7. distillationthe solvent was distilled off under reduced pressure
  8. concentrationwas concentrated under reduced pressure
  9. additionToluene was added to the obtained residue
  10. customthe precipitate was obtained by filtration

Quellen und Nachweise

ORD-Eintrag
ord-b7c104e09c184bc3bd36845d8574e5e4
Quelldatensatz
uspto-grants-2015_11
Patentnummer
US09187450B2

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