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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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HRID 1773855 반응식
[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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참가 물질

8

반응물 4

HCID 14798Sodium HydroxideHCID 660484-Piperidinol, 1-methyl-HCID 86703943HCID 86703943, 화합물HCID 86703944HCID 86703944, 화합물

생성물 2

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

시약·촉매·용매 2

HCID 962Water용매HCID 6395Methanesulfonic Acid용매

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-3226e26efe9240b5b5edd70ae695a27d
출처 데이터셋
uspto-grants-2016_02
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09255101B2

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