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

HRID 1773855Notes

Reaction equation

HRID 1773855 reaction equation
[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

Participants

8

Reactant 4

HCID 14798Sodium HydroxideHCID 660484-Piperidinol, 1-methyl-HCID 86703943HCID 86703943, compoundHCID 86703944HCID 86703944, compound

Product 2

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

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6395Methanesulfonic AcidSolvent

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-3226e26efe9240b5b5edd70ae695a27d
Source dataset
uspto-grants-2016_02
Patent number
US09255101B2

Reaction notes

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