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Sodium Hydroxide → 4-(1-methylpiperidin-4-yloxy)-2-trifluoromethyl-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulene

HRID 1773855
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Reaktionsgleichung

Reaktionsgleichung von HRID 1773855
[OH:1][CH:2]1[CH2:7][CH2:6][N:5]([CH3:8])[CH2:4][CH2:3]1.[CH2:9]([N:17]1[CH:21]=[C:20]([C:22]([F:25])([F:24])[F:23])[N:19]=[C:18]1[CH:26]=O)[CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.[CH2:28]([N:36]1[C:40]([C:41]([F:44])([F:43])[F:42])=[CH:39][N:38]=[C:37]1[CH:45]=[O:46])[CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1.[OH-].[Na+]>CS(O)(=O)=O.O>[CH3:8][N:5]1[CH2:6][CH2:7][CH:2]([O:1][CH:26]2[C:12]3[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=3[CH2:10][CH2:9][N:17]3[C:18]2=[N:19][C:20]([C:22]([F:25])([F:24])[F:23])=[CH:21]3)[CH2:3][CH2:4]1.[CH3:8][N:5]1[CH2:6][CH2:7][CH:2]([O:46][CH:45]2[C:31]3[CH:32]=[CH:33][CH:34]=[CH:35][C:30]=3[CH2:29][CH2:28][N:36]3[C:37]2=[N:38][CH:39]=[C:40]3[C:41]([F:44])([F:43])[F:42])[CH2:3][CH2:4]1
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Komponenten

8

Edukt 4

HCID 14798Sodium HydroxideHCID 660484-Piperidinol, 1-methyl-HCID 86703943HCID 86703943, VerbindungHCID 86703944HCID 86703944, Verbindung

Produkt 2

HCID 726956894-(1-methylpiperidin-4-yloxy)-2-trifluoromethyl-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulene
HCID 72695690
HCID 72695690, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 6395Methanesulfonic AcidLösungsmittel

Versuchsvorschrift

To a solution of 4-hydroxy-N-methylpiperidine (173 mg, 1.5 mmoles) in methanesulfonic acid (2.5 mL) is added a solution of the mixture of 1-phenethyl-4-trifluoromethyl-imidazole-2-carbaldehyde and 1-phenethyl-5-trifluoromethyl-imidazole-2-carbaldehyde (example 1B). The reaction mixture is stirred overnight at room temperature. Water is added and the mixture is basified to pH 9-10 with 12N NaOH. The aqueous phase is extracted three times with dichloromethane. The organic phase is dried over magnesium sulphate, filtered and the solvent is removed under reduced pressure. The residue is purified by silica gel chromatography using (CH2Cl2:MeOH:NH4OH) as eluent with a gradient from (99:5:0.1) to (95:5:0.5) to give pure 4-(1-methylpiperidin-4-yloxy)-2-trifluoromethyl-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulene (compound 1a) and pure 4-(1-methylpiperidin-4-yloxy)-1-trifluoromethyl-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulene (compound 1b).

Aufarbeitung

  1. extractionThe aqueous phase is extracted three times with dichloromethane
  2. dry with materialThe organic phase is dried over magnesium sulphate
  3. filtrationfiltered
  4. customthe solvent is removed under reduced pressure
  5. customThe residue is purified by silica gel chromatography

Quellen und Nachweise

ORD-Eintrag
ord-3226e26efe9240b5b5edd70ae695a27d
Quelldatensatz
uspto-grants-2016_02
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US09255101B2

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